Reduced Intensity Conditioning Transplant Using Haploidentical Donors

Study Overview
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Brief Summary
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This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.

Detailed Description
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Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 & 4 post-transplant.

Official Title
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Reduced Intensity Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies

Conditions
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Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Myelofibrosis, CMML, Multiple Myeloma, Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Melphalan
* Drug: Cyclophosphamide
* Procedure: peripheral blood stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction) Karnofsky status ≥70% One of the following high-risk malignancies: Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy Acute Myelogenous Leukemia in first or greater remission Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of <10%; CMML Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts <5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation Myeloproliferative diseases (myelofibrosis, CMML) Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors Exclusion Criteria: not be excluded on basis of sex, racial, or ethnic backgrounds poor cardiac function: left ventricular ejection fraction <40% poor pulmonary function: FEV1 and FVC <50% predicted poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy) poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) HIV-positive prior allogeneic transplant women of childbearing potential who currently are pregnant or who are not practicing adequate contraception any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up

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: Reduced-Intensity Mismatched Transplant<br>Fludarabine, Melphalan & Post-transplant cyclophosphamide | Drug: Fludarabine<br>* fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;<br>* Other names: Fludara;Drug: Melphalan<br> <br> * Other names: melphalan (140mg/m2) given one time on Day -1.;Drug: Cyclophosphamide<br>* cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.<br>* Other names: Cytoxan;Procedure: peripheral blood stem cell transplant<br> <br> * Other names: HSCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft Rejection | Measurement of donor cells vs. recipient cells | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Number of participants still alive 2 years after transplant | 2 years | 
| Relapse Incidence | Number of patients with disease reoccurrence at 1 and 2 years post-transplant | 2 years | 
| GVHD Incidence | The number of participants that developed graft-versus-host-disease before or at 100 days after transplant | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML, AML, MDS, ALL, CLL/CPL, HD, NHL, MPS, CMML, MM