Bone Marrow Transplantation in Young Adults With Severe Sickle Cell Disease (STRIDE)
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Purpose
The primary goal of this multicenter study is to determine the safety and feasibility of a Bone Marrow Transplantation (BMT) in young adults with severe sickle cell disease (SCD) using a reduced toxicity conditioning regimen consisting of busulfan (Bu)/ fludarabine (Flu)/ anti-thymocyte globulin (ATG). A two-component design will be used for this study. The first component will be restricted to patients who have an HLA-identical sibling donor. Five patients will be enrolled during the first component of the study. The second component of enrollment will include patients who have a related or an unrelated HLA-matched donor. Up to 10 additional patients will be enrolled in this component of the study.
| Condition | Intervention | Phase |
|---|---|---|
|
Sickle Cell Disease |
Other: Biological: Bone Marrow Transplant |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Hematopoietic Stem Cell Therapy for Young Adults With Severe Sickle Cell Disease |
- Event-free survival (EFS) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]To determine the safety and feasibility of a Bone Marrow Transplantation (BMT) in young adults with severe sickle cell disease (SCD) using a reduced toxicity conditioning regimen. Event-free survival (EFS) at one year after BMT will be evaluated by determining disease status, engraftment, and mortality.
- Transplant-related outcomes [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
The secondary objectives of this protocol are to evaluate the effect of a BMT on the clinical course of patients with severe SCD and determining the incidence of other transplant-related outcomes.
Specifically, to determine whether pre-transplant organ dysfunction (brain, heart, lung, kidney, liver, spleen, etc) due to SCD can be reversed after a BMT and the incidence of survival, engraftment, GVHD, and other transplant-related conditions.
| Estimated Enrollment: | 15 |
| Study Start Date: | March 2012 |
| Estimated Study Completion Date: | September 2015 |
| Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
-
Other: Biological: Bone Marrow Transplant
The bone marrow transplant regimen is below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant.
SCHEMA OF CONDITIONING REGIMEN Day Treatment (BU- Busulfan, FLU-Fludarabine, ATG-Rabbit Anti-thymocyte globulin)
Day -8 BU 3.2 mg/ kg/dose IV
Day -7 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV
Day -6 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 0.5mg/kg IV
Day -5 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 1.0mg/kg IV
Day -4 FLU 35mg/m2 IV, ATG 1.5mg/kg IV
Day -3 FLU 35mg/m2 IV, ATG 1.5mg/kg IV
Day -2 ATG 1.5mg/kg IV
Day -1 Rest
Day 0 Stem cell infusion
GVHD Regimen
Day -3 Calcineurin Inhibitor (Cyclosporine or Tacrolimus) therapeutic doses through day 180, then taper
Day 0 Stem cell infusion
Day +1 Methotrexate 7.5 mg/m2 IV
Day +3 Methotrexate 7.5 mg/m2 IV
Day +6 Methotrexate 7.5 mg/m2 IV
Day+11 Methotrexate 7.5 mg/m2 IV
Eligibility| Ages Eligible for Study: | 16 Years to 40 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diagnosis of severe sickle cell disease (Hb SS or Sß° Thalassemia) is denoted by one of the following:
- Clinically significant neurologic event or any neurological deficit lasting greater than 24 hours
- 2 or more episodes of acute chest syndrome in the last 2 years despite the use supportive care measures
- 3 or more severe vaso-occlusive pain episodes per year in the last 2 years despite supportive care measures
- Receives regular RBC transfusion therapy, defined as 8 or more transfusions per year for 1 year or longer
- Echocardiograph finding of Tricuspid Regurgitation Jet (TRJ) velocity of 2.7 m/sec or greater
- Adequate physical function
- Must have an 8 of 8 HLA-A, B, C, and DRB1 allele matched related or unrelated bone marrow donor
Exclusion Criteria:
- Patients with cirrhosis of the liver, uncontrolled bacterial, viral or fungal infection in the past month, or seropositivity for HIV
- Patients who have received prior HCT
- Females who are pregnant or breast feeding
Contacts and Locations| Contact: Lakshmanan Krishnamurti, MD | 412-692-6059 | krislx@chp.edu |
| Contact: Melissa A Byrne, MPH, RN | 412-692-7336 | Melissa.Jones@chp.edu |
| United States, California | |
| Children's Hospital of Oakland | Recruiting |
| Oakland, California, United States, 94609 | |
| Contact: Sandie Edwards 510-597-7169 SEdwards@mail.cho.org | |
| Principal Investigator: Mark C Walters, MD | |
| United States, Georgia | |
| Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Heather Renfroe Johnson, CCRC 404-778-5127 hrenfro@emory.edu | |
| Principal Investigator: Edmund Waller, MD | |
| Principal Investigator: James Eckman, MD | |
| United States, Pennsylvania | |
| Chidren's Hospital of Pittsburgh | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15224 | |
| Contact: Melissa A Byrne, MPH, RN 412-692-7336 Melissa.Jones@chp.edu | |
| Principal Investigator: Lakshmanan Krishnamurti, MD | |
| Principal Investigator: | Lakshmanan Krishnamurti, MD | Children's Hospital of Pittsburgh of UPMC |
More Information
Additional Information:
No publications provided
| Responsible Party: | Lakshmanan Krishnamurti, Principal Investigator, University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT01565616 History of Changes |
| Other Study ID Numbers: | PRO10110484, 1R34HL108761-01 |
| Study First Received: | March 26, 2012 |
| Last Updated: | January 18, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Pittsburgh:
|
Bone Marrow Transplant Severe Sickle Cell Disease HCT Hematopoietic Stem Cell Therapy Hematologic Diseases Genetic Diseases |
Anemia Hemolytic Congenital Human Leukocyte Antigen HLA |
Additional relevant MeSH terms:
|
Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia |
Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |
ClinicalTrials.gov processed this record on May 21, 2013