Clofarabine-Melphalan-Alemtuzumab Conditioning in Patients With Advanced Hematologic Malignancies

Study Overview
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Brief Summary
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This is a clinical research study designed to evaluate whether a conditioning regimen consisting of the combination of three drugs named melphalan, alemtuzumab and clofarabine supported by donor blood cells will result in rapid recovery and a high rate of long-lasting remissions in patients with leukemia, lymphoma and myeloma.

Official Title
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Clofarabine-melphalan-alemtuzumab Conditioning in Patients With Advanced Hematologic Malignancies

Conditions
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Advanced Hematologic Malignancies, Leukemia, Preleukemia

Intervention / Treatment
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* Drug: Clofarabine
* Drug: Melphalan
* Drug: Campath
* Procedure: Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory acute myelogenous or lymphoid leukemia Chronic myelogenous leukemia in accelerated phase or blast-crisis Chronic myelogenous leukemia in second or subsequent chronic phase Recurrent or refractory malignant lymphoma or Hodgkin's disease Multiple myeloma at high risk for disease recurrence Chronic lymphocytic leukemia, relapsed or with poor prognostic features Other Myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis) with poor prognostic features Myelodysplastic syndromes (including PNH) with > 5% blasts Zubroid performance status < 2 (See Appendix B) Life expectancy is not severely limited by concomitant illness Adequate cardiac and pulmonary function. Patients with decreased LVEF or PFTS will be evaluated by cardiology or pulmonary prior to enrollment on this protocol Calculated Creatinine Clearance > 50 ml/min Serum bilirubin 2.0 mg/dl, SGPT < 3x upper limit of normal No evidence of chronic active hepatitis or cirrhosis HIV-negative Patient is not pregnant Patient or guardian able to sign informed consent Exclusion Criteria: Clinical progression

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: Treatment<br> | Drug: Clofarabine<br>* Clofarabine will be administered as a 2-hour IV infusion on Days 1 through 5 at approximately the same time everyday (4 dose levels).<br>Drug: Melphalan<br>* Doses ranging from 100 to 140 mg/m2<br>Drug: Campath<br>* 20mg/d x5<br>Procedure: Stem Cell Transplant<br>* Infusion of donor, bone marrow and auto.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Hepatic Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Toxicity was scored according to NCI/CTC version 3 | Day 7 until Day 30 | 
| Number of Participants With Renal Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Toxicity was scored according to NCI/CTC version 3 | Day 7 until Day 30 | 
| Number of Participants With Skin Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Toxicity was scored according to NCI/CTC version 3 | Day 7 until Day 30 | 
| Number of Participants With Other Adverse Events During the Conditioning Regimen Prior to Stem Cell Transplantation | Toxicity was scored according to NCI/CTC version 3 | Day 7 until Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | 1 year | 
| Progression-free Survival (PFS) | Progression is defined from stem cell infusion to disease relapse, i.e., recurrence of hematologic malignancy and/or need for treatment after transplant for disease or death from any cause, whichever occurred first. | 1 year | 
| Treatment-related Mortality (TRM) |  | 1 year | 
| Relapse Rate |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melphalan, Alemtuzumab, Clofarabine