Trial Outcomes & Findings for Non-Myeloablative Conditioning and Bone Marrow Transplantation (NCT NCT01850108)
NCT ID: NCT01850108
Last Updated: 2024-01-10
Results Overview
Defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
NA
Target enrollment
26 participants
Primary outcome timeframe
at 1 year after BMT
Results posted on
2024-01-10
Participant Flow
Participant milestones
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Cyclophosphamide (CTX): Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Cyclophosphamide (CTX): Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Overall Study
Lost to Follow-up
|
4
|
|
Overall Study
Not eligible
|
1
|
|
Overall Study
Failed engraftment
|
2
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Non-Myeloablative Conditioning and Bone Marrow Transplantation
Baseline characteristics by cohort
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=26 Participants
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Cyclophosphamide (CTX): Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Age, Categorical
<=18 years
|
11 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=39 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
22 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=39 Participants
|
|
Region of Enrollment
United Kingdom
|
2 participants
n=39 Participants
|
|
Region of Enrollment
France
|
3 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: at 1 year after BMTPopulation: participants in this study
Defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy
Outcome measures
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=16 Participants
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Thiotepa: on Day -7 before BMT 10mg/kg (15 patients received this and one did not.)
Cyclophosphamide: Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Transplant-related Mortality (TRM)
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Participants in this study with median follow-up of 16.7 months (IQR, 6.5-30.8 months)
GVHD Severity was graded using the established National Institutes of Health's consensus criteria \[36\].
Outcome measures
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=16 Participants
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Thiotepa: on Day -7 before BMT 10mg/kg (15 patients received this and one did not.)
Cyclophosphamide: Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Number of Patients Who Developed Grade I-IV Acute Graft-vs.-Host Disease
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 180 after mini-haploBMTPopulation: Recipients of Haplo-BMT with PTCy and Thiotepa
Partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives. Defined in percentages of donor cells in patient's peripheral blood, measured in 4 ways. * Mixed donor chimerism: \> 0% but \< 95% * Complete donor chimerism \> 95% Any amount of donor chimerism after day 60 will be considered as having engrafted
Outcome measures
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=15 Participants
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Thiotepa: on Day -7 before BMT 10mg/kg (15 patients received this and one did not.)
Cyclophosphamide: Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Number of Patients With Donor Hematopoietic Chimerism in Peripheral Blood <95% at 6 Months After Mini-haploBMT
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 60 after BMTPopulation: Recipients of Haplo-BMT with PTCy and Thiotepa
Hematologic toxicity: -Absolute neutrophil count (ANC): consecutive values of \< 500/µL on 3 different days after chemotherapy post-BMT Platelet count: consecutive values of \< 20,000 µL on 3 different days after chemotherapy post-BMT Non-hematologic toxicities: -Toxicities necessitating hospitalization Toxicities grade 4 or above Meets the criteria of the following SAE: * Relapse of underlying disease * Grade 3 ocular toxicity not related to ocular GVHD * Grade 3 related non-hematologic toxicity
Outcome measures
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=16 Participants
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Thiotepa: on Day -7 before BMT 10mg/kg (15 patients received this and one did not.)
Cyclophosphamide: Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Mucositis
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Hepatic vessel clot
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
veno-occlusive disease of the liver
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
posterior reversible encephalopathy syndrome
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Platelet refractory thrombocytopenis
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Invasive fungal infection
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Mycophenolate mofetilinduced gastritis
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Duodenal ulcer-related gastrointestinal bleeding
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Typhilitis
|
1 Participants
|
|
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT
Encephalopathy
|
1 Participants
|
Adverse Events
Non-Myeloablative Conditioning and Bone Marrow Transplantation
Serious events: 9 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Non-Myeloablative Conditioning and Bone Marrow Transplantation
n=26 participants at risk
Thymoglobulin: Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV
Fludarabine: Days 6 and 2 before BMT: 30mg/m2/day IV
Cyclophosphamide (CTX): Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day
Mesna: Days 3 \& 4 after BMT: 40 mg/kg IV
Sirolimus: Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.
Mycophenolate mofetil (MMF): 15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT
Bone marrow transplantation: Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders
Total body irradiation: 200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted
|
|---|---|
|
Gastrointestinal disorders
Duodenal hemorrhage
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Nervous system disorders
Anaphylaxis
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome
|
7.7%
2/26 • Number of events 2 • Day 100 after transplant
|
|
General disorders
Fever
|
7.7%
2/26 • Number of events 2 • Day 100 after transplant
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seizure
|
7.7%
2/26 • Number of events 2 • Day 100 after transplant
|
|
Injury, poisoning and procedural complications
Fall
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Injury, poisoning and procedural complications
Hip fracture
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Nervous system disorders
Cognitive disturbancce
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Renal and urinary disorders
Kidney injury
|
7.7%
2/26 • Number of events 2 • Day 100 after transplant
|
|
General disorders
Generalized weakness
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Nervous system disorders
Depressed level of consciousness
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Sepsis
|
7.7%
2/26 • Number of events 2 • Day 100 after transplant
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Epstein-Barr virus viremia
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Vascular disorders
Hypotensive BSP
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Febrile w/elevated WBC
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Pneumonia
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Endocarditis
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Bacteremia
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Infections and infestations
Methicillin-resistant Staphylococcus aureus (MRSA)
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
|
Investigations
Acute Graft-Versus-Host Disease
|
3.8%
1/26 • Number of events 1 • Day 100 after transplant
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place