Haploidentical Transplantation With Pre-Transplant Immunosuppressive Therapy for Patients With Sickle Cell Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03279094|
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : February 14, 2018
This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease.
The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Biological: Hematopoietic stem cell transplantation||Phase 1|
All patients will receive an haploidentical hematopoietic stem cell transplant with the following conditioning and GvHD prevention:
Pre-transplant immunosuppressive therapy:
2 cycles of Fludarabine and Dexamethasone x 5 days each cycle
rATG daily x 3 days, Fludarabine daily x 6 days and Busulfan daily x 4 days
Cyclophosphamide day +3 and +4, Tacrolimus and Mycophenolate mofetil
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Pre-transplant Immunosuppressive Therapy for Haploidentical Transplants in Patients With Sickle Cell Disease|
|Actual Study Start Date :||February 2, 2018|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2023|
|Experimental: Haploidentical stem cell transplantation||
Biological: Hematopoietic stem cell transplantation
Haploidentical stem cell transplantation with pre-transplant immunosuppressive therapy
- Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT: [ Time Frame: 190 days ]
- Rate of death of any causes
- Rate of study discontinuation or early withdrawal
Rate of graft failure
• Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve <30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
- Rate of grade 4 non-hematological toxicities per NCI CTCAE v4.03 that last more than 21 days
- Time to donor neutrophil engraftment [ Time Frame: 24 months ]Day of Neutrophil Engraftment: The first of three consecutive days on which the ANC is ≥0.5x109/L
- Time to donor platelets engraftment [ Time Frame: 24 months ]Day of Platelet engraftment: The first documented day on which the platelet count is >20x109/L unsupported by platelet transfusions for 7 days
- Rate of graft failure [ Time Frame: 24 months ]Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve <30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
- Incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation [ Time Frame: 100 days after transplantation ]
- Incidence of chronic GvHD [ Time Frame: 24 months ]
- Overall survival rate [ Time Frame: 24 months ]• Overall survival: the time from start of PTIS to death, or last follow-up, whichever comes first.
- Event-free survival rate [ Time Frame: 24 months ]• Event-free survival: the time from start of PTIS to death, the unacceptable events, or last follow-up, whichever comes first.
- Disease free survival rate [ Time Frame: 24 months ]• Disease free survival: the time from HCT to death, secondary graft failure, or last follow-up, whichever comes first.
- Immune reconstitution at day 100, 180 and 365 [ Time Frame: 24 months ]• Immune reconstitution: measurement of CD3, CD4, CD8, CD11b, CD14, CD56, CD20/19, FoxP3+ Treg, and memory subsets.
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 from start of pre-transplant immunosuppressive therapy to 24 months post transplant [ Time Frame: 24 months post-transplant ]
- Percent of donor chimerism at 12 and 24 months after HCT [ Time Frame: 12 and 24 months after HCT ]
- Change From Baseline in Pain Scores using Numerical Rating Scale or Faces Pain Rating Scale at 100 days, 6 months and 12 months post-transplant [ Time Frame: 100 days, 6 months and 12 months 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): NCT03279094
|Contact: Anna B. Pawlowska, MDfirstname.lastname@example.org|
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Mary Suarez, CRC 626-218-5795 email@example.com|
|Principal Investigator: Anna B. Pawlowska, MD|
|Principal Investigator:||Anna B. Pawlowska, MD||City of Hope Medical Center|