Trial Outcomes & Findings for Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia (NCT NCT01772420)
NCT ID: NCT01772420
Last Updated: 2023-07-27
Results Overview
The number of patients demonstrating overall Hematologic Improvement (HI) was assessed based on the MDS 2006 IWG criteria. The IWG criteria for HI define specific responses of cytopenia in the 3 hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N) as demonstrated in corresponding outcome measures. Responses must have sustained for at minimum of 8 weeks for the participant to be included in the tally.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
Results posted on
2023-07-27
Participant Flow
From October 2012 through January 2020, 52 patients were enrolled in this multicenter study.
Participant milestones
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Overall Study
STARTED
|
16
|
15
|
21
|
|
Overall Study
COMPLETED
|
16
|
15
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia
Baseline characteristics by cohort
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
74 years
n=99 Participants
|
73 years
n=107 Participants
|
68 years
n=206 Participants
|
71 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
37 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
29 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic Black
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race/Ethnicity, Customized
Unknown (Not Documented)
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=99 Participants
|
15 participants
n=107 Participants
|
21 participants
n=206 Participants
|
52 participants
n=7 Participants
|
|
Baseline Hemoglobin
|
8.2 g/dL
n=99 Participants
|
8.1 g/dL
n=107 Participants
|
8.6 g/dL
n=206 Participants
|
8.4 g/dL
n=7 Participants
|
|
Baseline Platelet
|
257 platelets x10^9/L
n=99 Participants
|
134 platelets x10^9/L
n=107 Participants
|
19 platelets x10^9/L
n=206 Participants
|
126 platelets x10^9/L
n=7 Participants
|
|
Blast Count
|
1.96 percentage of blasts in bone marrow cell
n=99 Participants
|
1.87 percentage of blasts in bone marrow cell
n=107 Participants
|
1.8 percentage of blasts in bone marrow cell
n=206 Participants
|
1.87 percentage of blasts in bone marrow cell
n=7 Participants
|
|
Myelodysplastic Syndrome (MDS)
|
16 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
49 Participants
n=7 Participants
|
|
Chronic Myelomonocytic Leukemia (CMML)
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndrome (MDS)
Very Low Risk
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndrome (MDS)
Low Risk
|
8 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
24 Participants
n=7 Participants
|
|
Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndrome (MDS)
Intermediate Risk
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
27 Participants
n=7 Participants
|
|
Number of Prior Treatments
|
0.63 Prior Treatments
n=99 Participants
|
0.53 Prior Treatments
n=107 Participants
|
0.48 Prior Treatments
n=206 Participants
|
0.54 Prior Treatments
n=7 Participants
|
PRIMARY outcome
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 yearsPopulation: Intention to treat population study design.
The number of patients demonstrating overall Hematologic Improvement (HI) was assessed based on the MDS 2006 IWG criteria. The IWG criteria for HI define specific responses of cytopenia in the 3 hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N) as demonstrated in corresponding outcome measures. Responses must have sustained for at minimum of 8 weeks for the participant to be included in the tally.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Number of Patients Demonstrating Overall Hematologic Improvement (HI)
|
6 Participants
|
5 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 yearsPopulation: Intention to treat population study design.
The Number of Patients with Hematologic Improvement in Platelet Counts (HI-P) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an absolute increase of ≥ 30 × 10\^9/L (for those patients starting with \> 20 × 10\^9/L platelets) or an increase from \< 20 × 10\^9/L to \> 20 × 10\^9/L along with an increase of at least 100%, were deemed to have demonstrated HI-P improvement.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Number of Patients With Hematologic Improvement in Platelet Counts (HI-P)
|
0 Participants
|
3 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 yearsPopulation: Intention to treat population study design.
The Number of Patients with Hematologic Improvement in Erythrocyte Counts (HI-E) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an Hgb increase by ≥ 1.5 g/dL were deemed to have improvement in HI-E. Only transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Number of Patients With Hematologic Improvement in Erythrocyte Counts (HI-E)
|
6 Participants
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 yearsPopulation: Intention to treat population study design.
The Number of Patients with Hematologic Improvement in Neutrophil Counts (HI-N) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an increase of at least 100% and an absolute increase \> 0.5 × 10\^9/L were determined to have shown an improvement in HI-N.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Number of Patients With Hematologic Improvement in Neutrophil Counts (HI-N)
|
0 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 yearsPopulation: Intention to treat population study design.
Time to hematologic improvement as determined by median time required to achieve HI response.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Time to Attain Hematologic Improvement (HI)
|
12 number of weeks
Interval 2.4 to 16.0
|
8 number of weeks
Interval 2.0 to 20.0
|
8 number of weeks
Interval 6.0 to 12.4
|
SECONDARY outcome
Timeframe: Time to progression/relapse following hematologic improvement, at completion of final cycle and treatment discontinuation; up to 6 yearsPopulation: Intention to treat population study design.
Duration to hematologic improvement as determined by median duration of HI response.
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Duration of Hematologic Improvement (HI)
|
41 number of weeks
Interval 25.0 to 141.0
|
88 number of weeks
Interval 8.3 to 107.0
|
40 number of weeks
Interval 8.0 to 295.0
|
SECONDARY outcome
Timeframe: Treatment initiation through study completion, up to 2 yearsPopulation: Intention to treat population study design.
Number of Patients With Clinically Significant Bleeding Events
Outcome measures
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 Participants
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 Participants
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 Participants
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Number of Patients With Clinically Significant Bleeding Events
|
0 Participants
|
2 Participants
|
0 Participants
|
Adverse Events
Arm A (Platelets > 50,000 k/uL) LEN Initiation
Serious events: 8 serious events
Other events: 15 other events
Deaths: 1 deaths
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
Serious events: 5 serious events
Other events: 9 other events
Deaths: 2 deaths
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 participants at risk
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 participants at risk
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 participants at risk
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Infections and infestations
Sepsis
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Neutropenia
|
18.8%
3/16 • Number of events 3 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
20.0%
3/15 • Number of events 3 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Thrombocytopenia (severe)
|
12.5%
2/16 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
6.7%
1/15 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Infections and infestations
Lung Infection
|
0.00%
0/16 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
6.7%
1/15 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gall Bladder Cancer
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
Other adverse events
| Measure |
Arm A (Platelets > 50,000 k/uL) LEN Initiation
n=16 participants at risk
Patients with baseline platelet counts \>50,000 k/uL received lenalidomide (LEN) PO daily or QOD on days 1-21. If platelet counts fell below 50,000 k/uL during treatment, patients discontinued LEN and received eltrombopag olamine (ELT) PO daily or QOD until platelet counts \> 50,000 k/uL were achieved, and then maintained for 2 weeks thereafter. If a platelet count \>50,000 k/uL was maintained, patients discontinued ELT and resumed only LEN as a single agent (PO daily or QOD). If platelets fell below 50,000 k/uL a second time, LEN was stopped and ELT was re-initiated at the dose last given to the patient. Once platelet counts were \>50,000 k/uL and maintained for 2 weeks, patients resumed LEN concurrently with ELT for all subsequent courses.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination
n=15 participants at risk
Patients with baseline platelet counts \<50,000 k/uL received eltrombopag olamine (ELT) PO daily or QOD on days 1-28 until a platelet count \>50,000 k/uL was achieved. Once a platelet count\>50,000 k/uL was achieved the ELT dose was maintained for two weeks. After two weeks ELT was discontinued and LEN was started as in Arm A (i.e., eltrombopag olamine discontinued and lenalidomide started). Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Arm C (Platelets < 50,000 k/uL) ELT Monotherapy
n=21 participants at risk
Patients in Arm B were permitted to stay on ELT alone if a hematologic response on ELT was achieved as defined by the 2006 International Working Group (IWG) consensus criteria, or if baseline hemoglobin was \>10.0 g/dL and didn't decrease while on study drug.
Treatment repeated every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Eltrombopag Olamine: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
2/16 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Investigations
Blood Bilirubin Increased
|
0.00%
0/16 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
13.3%
2/15 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
4.8%
1/21 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Investigations
Acute Cholecystitis
|
12.5%
2/16 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
4.8%
1/21 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Vascular disorders
Hematoma
|
0.00%
0/16 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
4.8%
1/21 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Gastrointestinal disorders
Upper Gastrointestinal Hemorrhage
|
0.00%
0/16 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
4.8%
1/21 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
2/16 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
6.7%
1/15 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Neutropenia
|
25.0%
4/16 • Number of events 4 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
2/16 • Number of events 2 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
40.0%
6/15 • Number of events 6 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Renal and urinary disorders
Acute Kidney Injury
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16 • Number of events 1 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/15 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
0.00%
0/21 • Through study completion, up to 2 years
Adverse events categorized based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place