Non-Myeloablative Conditioning Regimen With Haploidentical T-Cell-Depleted Peripheral Blood Transplant for Patients With Severe Sickle Cell Disease
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|ClinicalTrials.gov Identifier: NCT03249831|
Recruitment Status : Recruiting
First Posted : August 15, 2017
Last Update Posted : February 14, 2018
Stem cells are made in the bone marrow, and can circulate the blood stream. These blood forming stem cells are collected from the blood stream (peripheral blood stem cells) or the bone marrow for transplant.
Blood stem cell transplants can be used to treat patients with sickle cell disease. In the future it is hoped that transplants may also be used to treat other health conditions like diabetes and auto-immune disease.
Transplant is often not an option for patients with other serious medical problems and most patients do not have a full-matched donor. Improving transplant success and reducing transplanted-related complications (like graft versus host disease) might allow more patients to get a transplant from a half-matched (haploidentical) donor (e.g. parent, sibling, and daughter/son).
This research transplant is being tested in this Pilot study for the first time and is different from a standard transplant because:
- Haploidentical donors will be used, and
- A new combination of drugs that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and
- Most of the donor CD4+ T cells (a type of immune cells) will removed (depleted) before giving the transplant to the patient.
After non-myeloablative conditioning treatment and haploidentical transplant, some of the blood cells in the recipient (patient) will be from the donor (mixed chimerism). Having the right mix of donor to recipient T cells can help improve haploidentical transplant outcomes.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease Sickle Cell Disorder Hemoglobinopathies Thalassemia Anemia, Sickle Cell||Drug: Cyclophosphamide Drug: Pentostatin Drug: Rabbit anti-thymocyte globulin Drug: Tacrolimus Drug: Mycophenolate mofetil Biological: CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Sickle Cell Disease Patients With COH-MC-17: a Non-Myeloablative, Conditioning Regimen and CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant|
|Anticipated Study Start Date :||June 2018|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||November 2021|
Experimental: COH-MC-17 and immunosuppressants
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.
Other Name: CytoxanDrug: Pentostatin
Other Name: NIPENTDrug: Rabbit anti-thymocyte globulin
Other Names:Drug: Tacrolimus
Initially IV. If patient tolerates, convert to oral.
Other Name: PROGRAF®Drug: Mycophenolate mofetil
IV or oral
Other Names:Biological: CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant
- Toxicity per NCI-Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Day -22 to 2 years post-transplant ]
- Unacceptable Toxicity at least possibly related to COH-MC-17 [ Time Frame: Day -22 to Day +60 post-transplant ]
- Mixed Chimerism defined as 30-90% donor cells [ Time Frame: Day +60 post-transplant ]
- Feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product [ Time Frame: From apheresis to Day 0 ]
- Adverse events of Grade 3 or higher [ Time Frame: Up to 2 years post-transplant ]
- Neutrophil count ≥ 500/mm3, time to recovery [ Time Frame: Up to 2 years post-transplant ]
- Platelet count ≥ 20,000/mm3, time to recovery [ Time Frame: Up to 2 years post-transplant ]
- Marrow failure [ Time Frame: Up to 2 years post-transplant ]
- Sickle cell disease related complications [ Time Frame: Up to 2 years post-transplant ]
- Non-relapse mortality [ Time Frame: Up to 2 years post-transplant ]
- Acute Graft versus Host Disease per 1994 Keystone Consensus Criteria [ Time Frame: Day + 100 post-transplant ]
- Chronic Graft versus Host Disease per 2014 National Institutes of Health Consensus Criteria [ Time Frame: Day+ 180, + 1 year and +2 years post-transplant ]
- Overall Survival [ Time Frame: Up to 2 years post-transplant ]
- Disease-Free Survival [ Time Frame: Up to 2 years post-transplant ]
- Event-Free Survival [ Time Frame: Up to 2 years post-transplant ]
- Disease Relapse [ Time Frame: Up to 2 years post-transplant ]
- Persistent post-immunosuppressant mixed chimerism [ Time Frame: 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 [ Time Frame: +2 years post-transplant ]Between 5% and 95% donor chimerism at two years post- transplant and on immunosuppressant
- Complete chimerism: >95% donor chimerism [ Time Frame: +2 years post-transplant ]
- Primary donor graft failure: Defined as < 5% donor chimerism by Day + 30 post- transplant [ Time Frame: Day +30 post-transplant ]
- Secondary donor graft failure: Defined as < 5% donor chimerism beyond Day +30 in patients with prior documentation of ≥ 5% donor cells by Day +30 [ Time Frame: > Day + 30 up to 2 years post-transplant ]
- Donor chimerism in blood [ Time Frame: Day +30, Day +60, Day +100, Day+180, and +1 yr, +1.5 yr, +2yr post-transplant ]
- Donor chimerism in bone marrow [ Time Frame: Day + 100, Day + 180 and + 1 yr post-transplant ]
- Percent HbS levels [ Time Frame: Baseline, and then Day + 30, Day + 100, Day + 180, +1 yr, +1.5, +2yr post-transplant ]
- Ratio donor: recipient de novo thymic T cells [ Time Frame: Up to 2 years post-transplant ]
- Ratio donor: recipient FoxP3+ regulatory T cells [ Time Frame: Up to 2 years post-transplant ]
- Tolerance status of donor: recipient type T cells [ Time Frame: Up to 2 years post-transplant ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03249831
|Contact: Joseph Rosenthal, MD||626-256-4673 ext firstname.lastname@example.org|
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Joseph Rosenthal, MD 626-256-4673 ext 88442 email@example.com|
|Principal Investigator: Joseph Rosenthal, MD|
|Principal Investigator:||Joseph Rosenthal, MD||City of Hope Medical Center|