Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States

Study Overview
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Brief Summary
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The purpose of this study is to look at whether the combination of lower-dose chemotherapy with two chemotherapy (anti-cancer) drugs, called busulfan and melphalan, and an antibody medication called alemtuzumab (Campath®), can prevent rejection of donor blood stem cells so that those cells take hold and build a healthy new blood cell factory after transplant. The study will also look at the safety of the combination of drugs and of the transplant of peripheral blood stem cells from a healthy relative or an unrelated donor.

Detailed Description
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Transplantation of related or unrelated allogeneic peripheral blood stem cells (PBSCs) after administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab will be associated with satisfactory engraftment and acceptable post-transplant non-relapse mortality.

Official Title
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A Phase II Study of Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT) for Treatment of Hematologic Malignancies and Hematopoietic Failure States

Conditions
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Hematologic Neoplasms, Multiple Myeloma, Anemia, Aplastic, Hemoglobinuria, Paroxysmal, Myelofibrosis

Intervention / Treatment
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* Drug: busulfan, and melphalan, and alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 to 75 years or age 18 to 49 with one or more of these risk factors: prior autologous, allogeneic or syngeneic HCT (Hematopoietic cell transplantation); not in first complete remission or first chronic phase; and/or presence of one or more medical conditions that would place the subject at high risk such as heart and kidney disease. Subjects with hematologic cancers must have received at least one previous course of chemotherapy or biological therapy. In other words, the subject cannot enroll in this trial for initial treatment of the disease. Availability of a healthy related or unrelated volunteer allogeneic donor. Exclusion Criteria: Eligible for another study or standard of care treatment that offers higher probability of cure or long-term control of subject's disease. Severe abnormal function of organs such as heart, kidneys, liver. Untreated or progressive central nervous system involvement by the disease. Subject is pregnant or breast-feeding. Performance score is below 50: at the least, requires considerable assistance and frequent medical care. Positive for the HIV [AIDS] virus Life expectancy less than 12 weeks with conventional treatments. For subjects capable of having children, refusal to practice birth control while on this study and for at least 12 months after PBSCT or after stopping post-transplant immunosuppressive treatments, whichever occurs later.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: busulfan, and melphalan, and alemtuzumab<br>Three drug regimen using busulfan, and melphalan, and alemtuzumab. | Drug: busulfan, and melphalan, and alemtuzumab<br>* intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). intravenous melphalan 100 mg/m2 on day -3. intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.<br>* Other names: Alemtuzumab (Campath®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT). | To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT). | Day +100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Relapse-free Survival. | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. | Day +100 | 
| Number of Participants With Event-free Survival. | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. | Day +100 | 
| Number of Participants With Overall Survival. | To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100. | Day +100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematologic malignancies, lymphoma, leukemia, MDS (myelodysplastic syndrome), reduced-intensity preparative regimen, allogeneic peripheral blood stem cell transplant, myelofibrosis or other myeloproliferative syndromes