A Blood Stem Cell Transplant for Sickle Cell Disease
- Conditions
- Sickle Cell DiseaseHemoglobinopathiesThalassemiaAnemia, Sickle CellSickle Cell Disorder
- Interventions
- Biological: CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant
- Registration Number
- NCT03249831
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the immune system (which fight infections) and platelets (which help the blood clot).
Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell transplant from a donor is a treatment option for patients with severe sickle cell disease. The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then make normal red blood cells - as well as other types of blood cells - in the patient. When blood cells from two people co-exist in the patient, this is called mixed chimerism.
Most children are successfully treated with blood stem cells from a sibling (brother/sister) who completely shares their tissue type (full-matched donor). However, transplant is not an option for patients who (1) have serious medical problems, and/or (2) do not have a full-matched donor. Most patients will have a relative who shares half of their tissue type (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical donor).
Adult patients with severe sickle cell disease were successfully treated with a half-matched transplant in a clinical study. Researchers would like to make half-matched transplant an option for more patients by (1) improving transplant success and (2) reducing transplanted-related complications.
This research transplant is being tested in this Pilot study for the first time. It is different from a standard transplant because:
1. Half-matched related donors will be used, and
2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and
3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted) before giving the blood stem cell transplant to the patient to improve transplant outcomes.
It is hoped that the research transplant:
1. Will reverse sickle cell disease and improve patient quality of life,
2. Will reduce side effects and help the patient recover faster from the transplant,
3. Help the patient keep the transplant longer and
4. Reduce serious transplant-related complications.
- Detailed Description
This is a pilot study to determine the safety and feasibility of the COH-MC-17 regimen and ability of the regimen to induce a mixed chimeric status in severe sickle cell disease patients (hemoglobin SS or S-βº Thalassemia). The COH-MC-17 regimen consists of a non-myeloablative regimen (cyclophosphamide, pentostatin and rabbit-anti-thymocyte globulin (ATG)) followed by a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant (HaploHCT).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description COH-MC-17 and immunosuppressants Rabbit anti-thymocyte globulin Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device. COH-MC-17 and immunosuppressants CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device. COH-MC-17 and immunosuppressants Cyclophosphamide Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device. COH-MC-17 and immunosuppressants Pentostatin Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device. COH-MC-17 and immunosuppressants Tacrolimus Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device. COH-MC-17 and immunosuppressants Mycophenolate mofetil Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device.
- Primary Outcome Measures
Name Time Method Mixed Chimerism defined as 30-90% donor cells Day +60 post-transplant Toxicity per NCI-Common Terminology Criteria for Adverse Events version 4.0 Day -22 to 2 years post-transplant Unacceptable Toxicity at least possibly related to COH-MC-17 Day -22 to Day +60 post-transplant Feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product From apheresis to Day 0
- Secondary Outcome Measures
Name Time Method Sickle cell disease related complications Up to 2 years post-transplant Acute Graft versus Host Disease per 1994 Keystone Consensus Criteria Day + 100 post-transplant Non-relapse mortality Up to 2 years post-transplant Disease Relapse Up to 2 years post-transplant Donor chimerism in bone marrow Day + 100, Day + 180 and + 1 yr post-transplant Platelet count ≥ 20,000/mm3, time to recovery Up to 2 years post-transplant Disease-Free Survival Up to 2 years post-transplant Adverse events of Grade 3 or higher Up to 2 years post-transplant Neutrophil count ≥ 500/mm3, time to recovery Up to 2 years post-transplant Marrow failure Up to 2 years post-transplant Event-Free Survival Up to 2 years post-transplant Persistent post-immunosuppressant mixed chimerism Up to 2 years post-transplant Between 5% and 95% donor chimerism at two years post- transplant, at least 6 months post- immunosuppressant
Persistent immunosuppressant -dependent mixed chimerism +2 years post-transplant Between 5% and 95% donor chimerism at two years post- transplant and on immunosuppressant
Secondary donor graft failure: Defined as < 5% donor chimerism beyond Day +30 in patients with prior documentation of ≥ 5% donor cells by Day +30 > Day + 30 up to 2 years post-transplant Donor chimerism in blood Day +30, Day +60, Day +100, Day+180, and +1 yr, +1.5 yr, +2yr post-transplant Overall Survival Up to 2 years post-transplant Complete chimerism: >95% donor chimerism +2 years post-transplant Chronic Graft versus Host Disease per 2014 National Institutes of Health Consensus Criteria Day+ 180, + 1 year and +2 years post-transplant Primary donor graft failure: Defined as < 5% donor chimerism by Day + 30 post- transplant Day +30 post-transplant Percent HbS levels Baseline, and then Day + 30, Day + 100, Day + 180, +1 yr, +1.5, +2yr post-transplant
Trial Locations
- Locations (1)
City of Hope Medical Center
🇺🇸Duarte, California, United States