Hematopoietic Stem Cell Transplant for 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: NCT02065596|
Recruitment Status : Recruiting
First Posted : February 19, 2014
Last Update Posted : February 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease Sickle Cell Anemia SCD||Drug: Fludarabine Procedure: Hematopoietic Stem Cell Transplant (HSCT)||Phase 1 Phase 2|
Hide Detailed Description
1. To evaluate the safety and feasibility of hematopoietic stem cell transplant (HSCT) after treatment with fludarabine in adult patients with Sickle Cell Disease (SCD).
Secondary Objective(s), in HSCT for SCD
- To evaluate the rates of disease-free and overall survival in both MSD and alternate graft donor (MUD, haploidentical, or cord blood-derived) recipients
- To evaluate fertility in matched sibling and alternate-donor graft recipients
- To evaluate GVHD rates in MSD and Alternate Graft Donor recipients in SCD.
- To evaluate cerebral, pulmonary, renal, and generalized vasculopathy before and after HSCT in SCD.
- To evaluate hematopoiesis and erythropoiesis before and before HSCT in SCD.
- Modulation of SCD Phenotype by Allogeneic Transplantation. Rigorous clinical follow-up will be performed, per routine care, to evaluate those consequences of SCD that will be modified by allogeneic transplantation in the short-term (4-12 weeks), in the medium-term (12-24 weeks) and in the long-term (>24 weeks). Short-term changes would include disappearance of stress hematopoiesis and erythropoiesis; medium- and long-term changes would include effects on pain, fertility (TSH, LH), cognition (routine cognitive assessments), and end-organ damage (including urine albumin-to-creatinine ratios and tricuspid regurgitant jet velocities, as indicated).
The study will start with at least 10 and up to 25 patients. They will be given the lowest starting dose of fludarabine. This is done to make sure it is safe. Researchers will watch the patients during what is called the dose-limiting toxicity (DLT) period. Their safety will be monitored by a Safety Monitoring Committee, which is made up of people who run research studies. The study will not take new patients until the DLT period is done.
If at least 3 of the 10 patients enrolled do not benefit, the maximum tolerated dose (MTD) will be considered exceeded. After the DLT period is complete, patients will receive a stem cell transplant from a genetically matched donor. Patients will be continued to be monitored for a year after the transplant.
To prepare for the transplant patients will have to undergo the following treatments:
- an exchange transfusion
a stem cell graft infusion from either a:
- perfectly matched sibling donor (called MSD),
- perfectly matched but unrelated donor (called MUD),
- a half-matched related donor (called Haploidentical), or
- a cord blood donor
- rabbit antithymocyte globulin (ATG)
- cytoxan (a type of chemotherapy)
- Fludarabine (you get this medicine a few weeks before transplant and again, as part of the routine chemotherapy treatment). This is the main drug being studies in this research
- total body irradiation (also called TBI)
- tacrolimus, mycophenolate (MMF) and/or methotrexate (MTX). These drugs will weaken your immune system. They are given to lower your chances of getting GVHD and rejecting the donor cells.
Patients will be in the study for approximately 14 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Hematopoietic Stem Cell Transplant for Sickle Cell Disease|
|Study Start Date :||April 24, 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: Immunomodulation with Fludarabine prior to HSCT
Fludarabine given beginning at 25mgm/m2 three times per day. Patients may be escalated up to 25mgm/m2 five times per day depending on dose-limiting toxicity
the study will begin with enrollment of an initial safety cohort of at least 10 subjects at the lowest dose, after which enrollment will pause until the dose-limiting toxicity (DLT) period has been completed. If a patient experiences DLT, defined as failure to engraft. In which case, the patient may be advanced to two higher doses.
Other Name: Fludarabine monophosphateProcedure: Hematopoietic Stem Cell Transplant (HSCT)
Three weeks after Immunomodulation patients will be infused with matched bone marrow from a sibling, unrelated donor, haploidentical donor, or cord blood. Patients will be followed for the following year.
- Probability of Engraftment [ Time Frame: 42 Days after transplant ]The number of patients with engraftment (as defined as recovery of ANC to 500 cells per cubic mm) compared to the total number of patients treated as a function of the patient's age.
- Mean time to engraftment [ Time Frame: 42 Days ]The average time to for engraftment (as defined as recovery of ANC to 500 cells per cubic mm) to occur estimated using a Kaplan-Meier curve as a function of the patient's age.
- Disease Progression [ Time Frame: 1 year ]The average time (in days) to disease progression estimated using a Kaplan-Meier curve
- Overall Survival [ Time Frame: 1 year ]The average time (in days) patients are alive after treatment estimated using a Kaplan-Meier curve
- Follicular Stimulating Hormone Levels [ Time Frame: 1 year ]Estimated difference in changes in Follicular Stimulating Hormone Levels after transplant, among patients with matched sibling donors compared to patients with alternate donors.
- Luteinizing Hormone Levels [ Time Frame: 1 year ]Estimated difference in changes in Luteinizing hormone Levels after transplant, among patients with matched sibling donors compared to patients with alternate donors.
- Testosterone Levels [ Time Frame: 1 year ]Estimated difference in changes in Testosterone Levels after transplant, among male patients with matched sibling donors compared to patients with alternate donors.
- Graft versus Host Disease [ Time Frame: 1 year ]The number patients with Grade III-IVGraft versus Host Disease as defined by CTCAE v4.0 in matched sibling compared to alternate-donor graft recipients
- Cerebral Vasculopathy [ Time Frame: 1 year ]Vasculopathy may clinically manifest as a history of stroke. The difference in number of strokes before and after transplantation will be evaluated with paired statistical tests (t-test or McNemar).
- Renal Vasculopathy [ Time Frame: 1 year ]Vasculopathy may clinically manifest as macroalbuminuria (≥300mg/g urinary albumin-to-creatinine ratio) or as a depressed estimated glomerular flow rate (eGFR). Evidence of renal vasculopathy before and after transplantation will be evaluated with paired statistical tests (t-test or McNemar).
- Pulmonary Vasculopathy [ Time Frame: 1 year ]Vasculopathy may clinically manifest as pulmonary arterial systolic pressure (PASP) by echo. Difference in PASP levels before and after transplantation will be evaluated with paired statistical tests (t-test or McNemar).
- Hematopoiesis [ Time Frame: 1 year ]Levels of stress hematopoiesis will be assessed by measuring telomere lengths with PCR before and after transplantation. These levels will be evaluated with paired statistical tests (t-test or McNemar).
- Erythropoiesis [ Time Frame: 1 year ]Levels of stress erythropoiesis will be assessed by measuring telomere lengths with PCR before and after transplantation. These levels will be evaluated with paired statistical tests (t-test or McNemar).
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): NCT02065596
|Contact: Jane Little, MDfirstname.lastname@example.org|
|United States, Ohio|
|University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Jane Little, MD 216-844-1272 email@example.com|
|Principal Investigator: Jane Little, MD|
|Principal Investigator:||Jane Little, MD||Case Comprehensive Cancer Center|