Trial Outcomes & Findings for HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity (NCT NCT02435901)

Results Overview

Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

1 year

Results posted on

2021-08-24

Participant Flow

There were no significant events in the study which prevented participant enrollment.

Participant milestones

Participant milestones
Measure	Reduced Intensity Regimen Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to s
Overall Study STARTED	29
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reduced Intensity Regimen n=29 Participants Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1
Age, Categorical <=18 years	28 Participants n=29 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=29 Participants
Age, Categorical >=65 years	0 Participants n=29 Participants
Sex: Female, Male Female	9 Participants n=29 Participants
Sex: Female, Male Male	20 Participants n=29 Participants
Hemoglobinopathies	29 Participants n=29 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All 29 participants were analyzed at time-points of 30 days, 100 days, 6 month and 1 year for sustained stem cell engraftment of donor cells.

Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.

Outcome measures

Outcome measures
Measure	Reduced Intensity Regimen n=29 Participants Alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. Day -1 Cyclosporine OR Tacrolimus along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the HLA matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to s
Number of Participants With Sustained Cell Engraftment of Donor Cells	29 Participants

SECONDARY outcome

Timeframe: 2 years

Patients will be evaluated for incidence and severity of graft versus host disease, infection, and cardiopulmonary complications.

Outcome measures

Outcome measures
Measure	Reduced Intensity Regimen n=29 Participants Alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. Day -1 Cyclosporine OR Tacrolimus along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the HLA matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to s
Assessment of Treatment Related Mortality and Morbidity Grade I-Grade III GVHD	13 Participants
Assessment of Treatment Related Mortality and Morbidity Chronic GVHD	9 Participants
Assessment of Treatment Related Mortality and Morbidity No complications	7 Participants

SECONDARY outcome

Timeframe: 2 years

29 participants will be evaluated for Event Free Survival.

Outcome measures

Outcome measures
Measure	Reduced Intensity Regimen n=29 Participants Alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. Day -1 Cyclosporine OR Tacrolimus along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the HLA matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to s
Event Free Survival; Number of Participants Who Survived at 2 Years Expired Secondary to Sepsis	1 Participants
Event Free Survival; Number of Participants Who Survived at 2 Years Expired Secondary to GVHD	2 Participants
Event Free Survival; Number of Participants Who Survived at 2 Years Survived Participants	26 Participants

Adverse Events

Reduced Intensity Regimen

Serious events: 3 serious events

Other events: 13 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Reduced Intensity Regimen n=29 participants at risk Alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. Day -1 Cyclosporine OR Tacrolimus along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. Day 0 the HLA matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 Mycophenolate mofetil: Immunosuppressant to prevent graft vs host
Gastrointestinal disorders Graft vs Host Disease	6.9% 2/29 • Number of events 2 • Adverse event data was collected up to the end of the first year post transplant. Serious adverse events included 3 participants who expired within the first year post transplant. One participant expired secondary to sepsis episode. Two participants expired secondary to complications of Grade III-IV graft vs. host disease. Adverse event included13 patients experienced adverse event of Grade I-II graft vs host disease, and responded to oral and/or topical treatment.
Infections and infestations Sepsis	3.4% 1/29 • Number of events 1 • Adverse event data was collected up to the end of the first year post transplant. Serious adverse events included 3 participants who expired within the first year post transplant. One participant expired secondary to sepsis episode. Two participants expired secondary to complications of Grade III-IV graft vs. host disease. Adverse event included13 patients experienced adverse event of Grade I-II graft vs host disease, and responded to oral and/or topical treatment.

Other adverse events

Other adverse events
Measure	Reduced Intensity Regimen n=29 participants at risk Alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. Day -1 Cyclosporine OR Tacrolimus along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. Day 0 the HLA matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. alemtuzumab (Campath IH): Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 Fludarabine: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. Melphalan: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. Cyclosporine: Immunosuppressant to prevent graft vs host disease is given on Day -1 Mycophenolate mofetil: Immunosuppressant to prevent graft vs host
Immune system disorders Grade I-II Graft vs Host Disease	44.8% 13/29 • Adverse event data was collected up to the end of the first year post transplant. Serious adverse events included 3 participants who expired within the first year post transplant. One participant expired secondary to sepsis episode. Two participants expired secondary to complications of Grade III-IV graft vs. host disease. Adverse event included13 patients experienced adverse event of Grade I-II graft vs host disease, and responded to oral and/or topical treatment.

Additional Information

Indira Sahdev, MD

Northwell Health System Cohen Children's Medical Center of NY

Phone: 7184703460

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place