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HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

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ClinicalTrials.gov Identifier: NCT02435901
Recruitment Status : Completed
First Posted : May 6, 2015
Results First Posted : November 5, 2020
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
Indira Sahdev, Northwell Health

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Sickle Cell Disease
Beta Thalassemia-Major
Interventions Drug: alemtuzumab (Campath IH)
Drug: Fludarabine
Drug: Melphalan
Drug: Cyclosporine
Drug: Mycophenolate mofetil
Drug: Tacrolimus
Biological: Hematopoietic Stem Cell Transplantation
Enrollment 29
Recruitment Details  
Pre-assignment Details There were no significant events in the study which prevented participant enrollment.
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description

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

Period Title: Overall Study
Started 29
Completed 29
Not Completed 0
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description

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

Overall Number of Baseline Participants 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
<=18 years
28
  96.6%
Between 18 and 65 years
1
   3.4%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
Female
9
  31.0%
Male
20
  69.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Hemoglobinopathies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
29
 100.0%
1.Primary Outcome
Title Number of Participants With Sustained Cell Engraftment of Donor Cells
Hide Description 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.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 29
Measure Type: Count of Participants
Unit of Measure: Participants
29
 100.0%
2.Secondary Outcome
Title Assessment of Treatment Related Mortality and Morbidity
Hide Description Patients will be evaluated for incidence and severity of graft versus host disease, infection, and cardiopulmonary complications.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description:

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. 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

Overall Number of Participants Analyzed 29
Measure Type: Count of Participants
Unit of Measure: Participants
Grade I-Grade III GVHD
13
  44.8%
Chronic GVHD
9
  31.0%
No complications
7
  24.1%
3.Secondary Outcome
Title Event Free Survival; Number of Participants Who Survived at 2 Years
Hide Description 29 participants will be evaluated for Event Free Survival.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description:

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. 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

Overall Number of Participants Analyzed 29
Measure Type: Count of Participants
Unit of Measure: Participants
Expired Secondary to Sepsis
1
   3.4%
Expired Secondary to GVHD
2
   6.9%
Survived Participants
26
  89.7%
4.Secondary Outcome
Title Immunological Reconstitution
Hide Description Measure the rate of T and B cell immune reconstitution by laboratory studies at 8 weeks, 6 months, one year and two years post transplant.
Time Frame 2 years
Outcome Measure Data Not Reported
Time Frame Adverse event data was collected up to the end of the first year post transplant.
Adverse Event Reporting Description

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.

 
Arm/Group Title Reduced Intensity Regimen
Hide Arm/Group Description

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

All-Cause Mortality
Reduced Intensity Regimen
Affected / at Risk (%)
Total   3/29 (10.34%)    
Hide Serious Adverse Events
Reduced Intensity Regimen
Affected / at Risk (%) # Events
Total   3/29 (10.34%)    
Gastrointestinal disorders   
Graft vs Host Disease * [1]  2/29 (6.90%)  2
Infections and infestations   
Sepsis *  1/29 (3.45%)  1
*
Indicates events were collected by non-systematic assessment
[1]
22 participants experienced various grades of graft vs host disease (GVHD), inclusive of skin & gut (acute and chronic). Of the 22, 2 participants expired from complication of graft vs host disease and 1 participant expired from a septic episode.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Reduced Intensity Regimen
Affected / at Risk (%) # Events
Total   13/29 (44.83%)    
Immune system disorders   
Grade I-II Graft vs Host Disease * [1]  13/29 (44.83%) 
*
Indicates events were collected by non-systematic assessment
[1]
13 patients experienced adverse event of Grade I-II graft vs host disease, and responded to oral and/or topical treatment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Indira Sahdev, MD
Organization: Northwell Health System Cohen Children's Medical Center of NY
Phone: 7184703460
EMail: isahdev@northwell.edu
Layout table for additonal information
Responsible Party: Indira Sahdev, Northwell Health
ClinicalTrials.gov Identifier: NCT02435901    
Other Study ID Numbers: 08057
First Submitted: April 24, 2015
First Posted: May 6, 2015
Results First Submitted: December 11, 2019
Results First Posted: November 5, 2020
Last Update Posted: November 5, 2020