A Study of Bone Marrow Transplantation Using Fully-Matched Relatives as Donors for Patients With Hematological Malignancies

Study Overview
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Brief Summary
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This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.

Detailed Description
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This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.

Official Title
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A Two Step Approach To Matched-Sibling Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematological Malignancies

Conditions
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Hematological Malignancies, Leukemia, Lymphoma, Multiple Myeloma, Hodgkin's Disease

Intervention / Treatment
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* Device: Matched Sibling Allogeneic Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients will be considered high-risk if they have any of the following: Age > 50 years ECOG Performance status of <2 Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL CML 2nd chronic phase, accelerated phase, or blastic phase MDS with IPS of Intermediate 2 or greater Any myeloproliferative disorder Hodgkin lymphoma: relapsed, refractory, or primary induction failure Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT Other conditions not listed will be assessed as high-risk by the PI Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci. Patients must adequate organ function: LVEF of >45% DLCO (adjusted for hemoglobin) >45% of predicted Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal Creatinine clearance of > 60 ml/min Patients must be willing to use contraception if they have childbearing potential Able to give informed consent Exclusion Criteria: ECOG performance status of 3 or 4. HIV positive Active involvement of the central nervous system with malignancy Psychiatric disorder that would preclude patients from signing an informed consent Pregnancy Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Transplantation<br>Matched Sibling Allogeneic Transplantation | Device: Matched Sibling Allogeneic Transplantation<br>* Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization<br>* Other names: CliniMACS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Overall Survival | The primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol. | 1 Year after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft Versus Host Disease (GVHD) |  | 1 Year after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloablative Hematopoietic Stem Cell Transplant, Cyclophosphamide tolerization, 2 Step Approach, Hematological malignancies, leukemia, lymphoma, multiple myeloma, Hodgkin's Disease