Trial Outcomes & Findings for Rituximab + High-Dose Methylprednisolone Debulking Prior to Venetoclax for CLL & SLL Patients (NCT NCT04981912)
NCT ID: NCT04981912
Last Updated: 2025-10-15
Results Overview
Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 1 or 2 cycles of HDMP + Rituximab. Low Tumor Burden = All measurable lymph nodes with the largest diameter \< 5 cm by radiologic assessment AND ALC \< 25k/uL Medium Tumor Burden = Any measurable lymph node with the largest diameter \>/= 5 cm but \< 10 cm by radiographic assessment OR ALC \>/= 25k/uL High Tumor Burden = Any measurable lymph node with the largest diameter \>/= 10 cm by radiologic assessment OR ALC \>/= 25k/uL AND any measurable lymph node with the largest diameter \>/= 5 cm
ACTIVE_NOT_RECRUITING
PHASE1
4 participants
28 or 56 days
2025-10-15
Participant Flow
This study accrued four patients in total.
The the pre-planned sample size was 17.
Participant milestones
| Measure |
Arm A
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Arm A
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Overall Study
Physician Decision
|
2
|
Baseline Characteristics
Rituximab + High-Dose Methylprednisolone Debulking Prior to Venetoclax for CLL & SLL Patients
Baseline characteristics by cohort
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=99 Participants
|
|
Age, Continuous
|
69 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Prior Lines of Therapy
|
1.5 Lines
n=99 Participants
|
PRIMARY outcome
Timeframe: 28 or 56 daysPopulation: All participants who received at least one dose of treatment.
Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 1 or 2 cycles of HDMP + Rituximab. Low Tumor Burden = All measurable lymph nodes with the largest diameter \< 5 cm by radiologic assessment AND ALC \< 25k/uL Medium Tumor Burden = Any measurable lymph node with the largest diameter \>/= 5 cm but \< 10 cm by radiographic assessment OR ALC \>/= 25k/uL High Tumor Burden = Any measurable lymph node with the largest diameter \>/= 10 cm by radiologic assessment OR ALC \>/= 25k/uL AND any measurable lymph node with the largest diameter \>/= 5 cm
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Percentage of Patients That Have a Decrease in Tumor Burden From Medium or High to Low
|
2 Participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All participants who received at least one dose of treatment.
Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 1 cycle of HDMP + Rituximab. Low Tumor Burden = All measurable lymph nodes with the largest diameter \< 5 cm by radiologic assessment AND ALC \< 25k/uL Medium Tumor Burden = Any measurable lymph node with the largest diameter \>/= 5 cm but \< 10 cm by radiographic assessment OR ALC \>/= 25k/uL
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Percentage of Patients That Have a Decrease in Tumor Burden From Medium to Low
|
2 Participants
|
SECONDARY outcome
Timeframe: 56 daysPopulation: All participants who received at least one dose of treatment.
Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 2 cycles of HDMP + Rituximab Low Tumor Burden = All measurable lymph nodes with the largest diameter \< 5 cm by radiologic assessment AND ALC \< 25k/uL Medium Tumor Burden = Any measurable lymph node with the largest diameter \>/= 5 cm but \< 10 cm by radiographic assessment OR ALC \>/= 25k/uL High Tumor Burden = Any measurable lymph node with the largest diameter \>/= 10 cm by radiologic assessment OR ALC \>/= 25k/uL AND any measurable lymph node with the largest diameter \>/= 5 cm
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Percentage of Patients That Have a Decrease in Tumor Burden if 2 Cycles of HDMP + Rituximab
|
2 Participants
|
SECONDARY outcome
Timeframe: 2.15 yearsPopulation: All participants who received at least one dose of treatment.
Rate of laboratory TLS (from start of treatment until completion of venetoclax ramp-up)
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Rate of Laboratory TLS (Tumor Lysis Syndrome)
|
0 Participants
|
SECONDARY outcome
Timeframe: 2.15 yearsPopulation: All participants who received at least one dose of treatment.
Rate of clinical TLS (from start of treatment until completion of venetoclax ramp-up)
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Rate of Clinical TLS
|
0 Participants
|
SECONDARY outcome
Timeframe: 2.15 yearsPopulation: All participants who received at least one dose of treatment.
Number of patients with non-hematological treatment-related adverse events by CTCAE4 definitions of grade 3 or higher, regardless of attribution
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Adverse Events by CTCAE4 Definitions
Number of patients with non-hematological treatment-related adverse events of grade 3 or higher · Grade 3 or higher, related to treatment
|
1 Participants
|
|
Adverse Events by CTCAE4 Definitions
Number of patients with non-hematological treatment-related adverse events of grade 3 or higher · < Grade 3, related or unrelated to treatment
|
2 Participants
|
|
Adverse Events by CTCAE4 Definitions
Number of patients with non-hematological treatment-related adverse events of grade 3 or higher · No AEs
|
1 Participants
|
|
Adverse Events by CTCAE4 Definitions
Number of patients with hematological treatment-related adverse events of grade 3 or higher · Grade 3 or higher, related to treatment
|
0 Participants
|
|
Adverse Events by CTCAE4 Definitions
Number of patients with hematological treatment-related adverse events of grade 3 or higher · < Grade 3, related or unrelated to treatment
|
3 Participants
|
|
Adverse Events by CTCAE4 Definitions
Number of patients with hematological treatment-related adverse events of grade 3 or higher · No AEs
|
1 Participants
|
SECONDARY outcome
Timeframe: 9 months and at end of study up to 3 yearsPopulation: All participants who received at least one dose of treatment.
Overall Response rate, Partial Response rate, and Complete response rate per iwCLL criteria after 9 months of venetoclax and at completion of treatment Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Response Rates
Overall response rate around 9 months · Partial response
|
0 Participants
|
|
Response Rates
Overall response rate around 9 months · Complete response
|
2 Participants
|
|
Response Rates
Overall response rate around 9 months · Other
|
2 Participants
|
|
Response Rates
Overall response rate over the course of the study · Partial response
|
1 Participants
|
|
Response Rates
Overall response rate over the course of the study · Complete response
|
2 Participants
|
|
Response Rates
Overall response rate over the course of the study · Other
|
1 Participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All participants who received at least one dose of treatment.
Undetectable minimal residual disease (MRD) rate based on bone marrow biopsy after 9 months of venetoclax, and at completion of treatment
Outcome measures
| Measure |
Arm A
n=4 Participants
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Undetectable Minimal Residual Disease (MRD) Rate
Undetectable MRD at 9 months · Undetectable MRD
|
2 Participants
|
|
Undetectable Minimal Residual Disease (MRD) Rate
Undetectable MRD at 9 months · Detectable
|
2 Participants
|
|
Undetectable Minimal Residual Disease (MRD) Rate
Overall response rate over the course of the study · Undetectable MRD
|
3 Participants
|
|
Undetectable Minimal Residual Disease (MRD) Rate
Overall response rate over the course of the study · Detectable
|
1 Participants
|
Adverse Events
Arm A
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm A
n=4 participants at risk
HDMP + rituximab as a means of debulking prior to initiating venetoclax.
HDMP + rituximab as a means of debulking prior to initiating venetoclax.: - Patients will receive HDMP + Rituximab for 1 cycle, followed by reassessment of Tumor Burden,
* If Tumor Burden classification is low after HDMP + Rituximab (lymph nodes \< 5cm in diameter AND absolute lymphocyte count \< 25k/uL), patients will initiate venetoclax dose ramp-up, with ramp-up schedule according to venetoclax package insert.
* Patients who still have a disease burden (lymphadenopathy \> 5 cm or ALC \> 25k/iL) that meets criteria for medium or high risk of TLS after 1 cycle of HDMP + Rituximab are given the option to repeat a 2nd cycle of HDMP + Rituximab prior to venetoclax dose ramp-up.
|
|---|---|
|
Ear and labyrinth disorders
Ear and Labyrinth disorders - other
|
25.0%
1/4 • Number of events 2 • 3 years
|
|
Ear and labyrinth disorders
Vertigo
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 2 • 3 years
|
|
General disorders
Edema limbs
|
50.0%
2/4 • Number of events 2 • 3 years
|
|
General disorders
Edema trunk
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
General disorders
Fever
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
General disorders
General disorders and administration site conditions - Other
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
General disorders
Infusion related reaction
|
50.0%
2/4 • Number of events 3 • 3 years
|
|
Infections and infestations
Upper respiratory infection
|
25.0%
1/4 • Number of events 2 • 3 years
|
|
Injury, poisoning and procedural complications
Bruising
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Nervous system disorders
Headache
|
50.0%
2/4 • Number of events 2 • 3 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
25.0%
1/4 • Number of events 1 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
25.0%
1/4 • Number of events 1 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place