Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide

Study Overview
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Brief Summary
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Historically, the best results of allogeneic SCT have been obtained when the stem cell donor is a human leukocyte antigen (HLA)-matched sibling, however, this is only available for approximately 30 percent of patients in need for SCT. Alternative donor sources include matched unrelated donor utilizing the donor registry, cord blood transplant and mismatched donor transplant. A human leukocyte antigen (HLA)-haploidentical donor is one who shares, by common inheritance, exactly one HLA haplotype with the recipient, and includes the biologic parents, biologic children and full or half siblings. There is strong body of evidence supporting the use of haplo-SCT in patient who lack a matched sibling or unrelated donor with high rates of successful engraftment, effective Graft Versus Host Disease (GVHD) control and favorable outcomes comparative to those seen using other allograft sources, including HLA-matched sibling SCT. Furthermore, it provides a cost-efficient donor option in a timely manner especially for patients who need to proceed quickly to transplant due to concern of disease relapse/progression.

Detailed Description
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An open label, single-arm, single-center study to evaluate the safety, efficacy and feasibility of haplo-SCT as an alternative donor source for patients who lack a matched sibling/unrelated donor options. The choice of the chemotherapy treatment for transplantation will be up to the investigator. Post-transplant cyclophosphamide will serve as the backbone of the immunosuppression treatment to prevent GVHD. GVHD Prevention Treatment: Cyclophosphamide will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus will be administered IV until patient can take it by mouth starting on day of transplant and continue approximately 100 days post-transplant. Mycophenolate mofetil will be administered IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.

Official Title
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Safety, Efficacy and Feasibility of Haploidentical Stem Cell Transplantation (Haplo-SCT) Using Post-Transplant Cyclophosphamide (PTCy) as an Alternative Donor Source for Patients Who Lack a Matched Sibling/Unrelated Donor Options

Conditions
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Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome, Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Tacrolimus
* Drug: Mycophenolate mofetil
* Other: Haploidentical Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 16 years old and up Performance Status 70 percent or above Patients should have the following diseases: Acute myelogenous leukemia (AML) Acute lymphocytic leukemia or lymphoblastic lymphoma (ALL) Transfusion dependent myelodysplastic syndrome (MDS) Non-Hodgkin's Lymphoma (NHL) Chronic lymphocytic leukemia (CLL) Pulmonary function as measured by forced expiratory volume at one second (FEV1) and/or corrected diffusing capacity of lung for carbon monoxide (DLCO) at 60 percent of predicted or above Left ventricular ejection fraction at 45 percent or above If the donor-specific HLA antibodies (DSA) are positive, the patient must undergo a desensitization protocol resulting in undetectable DSA prior to day of transplant Exclusion Criteria: Less than twenty-one days have elapsed since the subject's last radiation or chemotherapy prior to conditioning (except for hydroxyurea) Uncontrolled bacterial, fungal or viral infections at time of study enrollment Positive for HIV, human T-cell leukemia virus (HTLV-1) and/or Hepatitis C Subjects with signs/symptoms of active central nervous system (CNS) disease

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients will receive Haploidentical<br>The choice of the chemotherapy treatment for transplantation will be up to the investigator. Post-transplant cyclophosphamide will serve as the backbone of the immunosuppression treatment to prevent GVHD. All patients will receive a Haplo-identical stem cell transplantation. GVHD Prevention Treatment: Cyclophosphamide 50mg/kg will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth starting on day of transplant and continue approximately 100 days post-transplant. Mycophenolate mofetil 15mg/kg will be administered twice a day IV until patient can take it by mouth starting on Day 1 post transplant until 28 days. | Drug: Cyclophosphamide<br>* IV medication given for prevention of graft versus host disease.<br>* Other names: Cytoxan;Drug: Tacrolimus<br>* IV medication given for prevention of graft versus host disease.<br>* Other names: Prograf;Drug: Mycophenolate mofetil<br>* IV medication given for prevention of graft versus host disease.<br>* Other names: Cellcept;Other: Haploidentical Stem Cell Transplantation<br>* A stem cell transplant that involves matching a patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type, with that of a related donor.<br>* Other names: Haploidentical hematopoietic stem cell transplantation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chimerism | Blood test that measures amount of donor's cells | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil engraftment | Blood test that measures the white cell count | Day 28 | 
| Platelet engraftment | Blood test that measures the platelet count | Day 60 | 
| Grade 3 to 4 acute graft-verus-host disease (GVHD) | National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form | 100 days | 
| Frequency and severity of chronic GVHD | National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form | 1 year | 
| Disease status with blast counts (immature blood cell count) above 5% | Blood work and/or bone marrow biopsy will be used | 3 years | 
| Survival status by patient contact | Contact with patient by phone or doctor's visit | 3 years | 
| Immune reconstitution | Blood work will be used to evaluate recovery of T and B cell count subset that assess cells which make antibodies to fight infections | 3 years | 
| Grade 3 through 5 Adverse Events | Toxicities that are possibly, probably, and definitely related to study treatment according to NCI CTCAE Version 4 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Non-Hodgkin Lymphoma, Haploidentical, Bone Marrow Transplant, Stem Cell Transplant, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome, Chronic Lymphocytic Leukemia, GVHD