Plerixafor and Filgrastim For Mobilization of Donor Peripheral Blood Stem Cells Before A Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Study Overview
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Brief Summary
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RATIONALE: Giving chemotherapy and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they will help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving colony-stimulating factors, such as filgrastim (G-CSF) and plerixafor, to the donor helps the stem cells move (mobilization) from the bone marrow to the blood so they can be collected and stored. PURPOSE: This clinical trial is studying giving plerixafor and filgrastim together for mobilization of donor peripheral blood stem cells before a peripheral blood stem cell transplant in treating patients with hematologic malignancies

Detailed Description
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PRIMARY OBJECTIVES: I. The percentage of normal donors who collect at least 2 x 10^6 CD34 cells/kg recipient weight on day 1 after administration of combined filgrastim and plerixafor. SECONDARY OBJECTIVES: I. Measuring CD34+ cells/ul in peripheral blood of donors 11, 15, 24 and 36 hours post dosing. II. Tolerance and safety of combined filgrastim and Plerixafor in normal donors. III. Engraftment of filgrastim/plerixafor mobilized stem cells in allogeneic recipients. IV. Acute and chronic graft-versus-host disease (GVHD) following the use of filgrastim/plerixafor mobilized stem cells. V. Yield of CD34+ cells based on donor weight. OUTLINE: Donors receive filgrastim subcutaneously (SC) and plerixafor SC on day -14 and undergo leukapheresis to collect peripheral blood stem cells (PBSC) on day -13. These cells are frozen to preserve them. Treatment modifications may apply according to sufficient collection of PBSC. Patients receive standard high-dose conditioning and undergo allogeneic PBSC transplantation on day 0 using the previously frozen cells. After completion of study treatment, donors are followed up 1 day after the last stem cell donation.

Official Title
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A Pilot Study of Combined Plerixafor + Filgrastim for Mobilization of Peripheral Blood Stem Cells From Normal Donors

Conditions
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Recurrent Mantle Cell Lymphoma, Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Atypical Chronic Myeloid Leukemia, BCR-ABL Negative, Blastic Phase Chronic Myelogenous Leukemia, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: plerixafor
* Biological: filgrastim
* Procedure: peripheral blood stem cell transplantation
* Procedure: allogeneic hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hematologic malignancy considered eligible and suitable for allogeneic stem cell transplantation (syngeneic transplantation is acceptable); diagnoses include acute myeloid or lymphoid leukemias, chronic myeloid or lymphoid leukemias, multiple myeloma, lymphoma or myelodysplasia; subjects suitable for this study will primarily receive transplant on a standard treatment plan (non research regimen) Organ function, performance status and age suitable for an ablative regimen consisting of TBI >= 10Gy or a chemotherapy regimen consisting of busulphan and cyclophosphamide (BuCY) or busulphan and melphalan (BuMel) Availability of a fully matched sibling donor Ability to understand and willingness to sign an informed consent No uncontrolled infections DONOR: Human leukocyte antigen (HLA) identical sibling donor DONOR: >= 18 years DONOR: No unacceptable risk to donor due to pre-existing illness DONOR: Must have suitable antecubital veins for leukapheresis venipuncture; donors who will require a temporary, Mahurkar-type catheter are not eligible DONOR: Ability and willingness to sign an informed consent document Exclusion Criteria: Eligible for and willingness to participate in any research study of transplant regimens Eligible for and willingness to participate in a non ablative transplant regimen Human immunodeficiency virus (HIV) seropositive Pregnancy DONOR: HIV seropositive DONOR: Contraindication or hypersensitivity to filgrastim or plerixafor DONOR: Hepatitis A, B, C seropositive DONOR: Pregnant or lactating females DONOR: Liver function studies > 2 times the upper limit of normal (ULN) at evaluation, Creatinine > 2, pulmonary function diffusing lung capacity for carbon monoxide (DLCO) < 50% (if specifically evaluated), cardiac ejection fraction < 50% (if specifically evaluated) DONOR: Any known ventricular arrhythmia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Filgrastim and plerixafor for PBSC mobilization<br>Donors receive filgrastim subcutaneously (SC) and plerixafor SC on day -14 and undergo leukapheresis to collect peripheral blood stem cells (PBSC) on day -13. These cells are frozen to preserve them. Treatment modifications may apply according to sufficient collection of PBSC. Patients receive standard high-dose conditioning and undergo allogeneic PBSC transplantation on day 0 using the previously frozen cells. After completion of study treatment, donors are followed up 1 day after the last stem cell donation. | Drug: plerixafor<br>* Given SC<br>* Other names: Mozobil;Biological: filgrastim<br>* Given SC<br>* Other names: Neupogen;Procedure: peripheral blood stem cell transplantation<br>* Infusion of peripheral blood stem cells<br>* Other names: transplantation, peripheral blood stem cell;Procedure: allogeneic hematopoietic stem cell transplantation<br>* Infusion of hematopoietic stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful Collection of Stem Cells | Percentage of donors from whom at least 2 x 10^6 CD34+ cells/kg body weight were collected based on actual recipient body weight | At the end of apheresis for cell collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD34-positive Cells Collected | Number of CD34-positive cells collected per kg recipient body weight | At the end of apheresis for cell collection |