Granulocyte Colony-stimulating Factor (G-CSF) Plus or Minus AMD3100 for Engraftment Post Allogeneic Transplant

Study Overview
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Brief Summary
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Patients who have not had adequate blood count recovery post related or unrelated stem cell transplant will be given a boost of T-cell depleted, enriched stem cells to hopefully improve their blood counts.

Detailed Description
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Patients who have not had adequate blood count recovery post related or unrelated stem cell transplant will be given a boost of T-cell depleted, enriched stem cells to hopefully improve their blood counts. The unrelated donors will receive G-CSF prior to pheresis (collection of the stem cells) to boost the number of CD34+ cells. The related donors will receive G-CSF and AMD3100 prior to pheresis to boost the number of CD34+ cells. Once the CD34+ cells are collected they will be T-cell depleted using a cell separation device called the CliniMACS systems. The CliniMACS system will select the CD34+ cell and remove the T-cells. By removing the T-cells we can minimize the risk of Graft Versus Host Disease (GVHD). The enriched CD34+ cells will be given to them to hopefully give them a boost of cells that can permanently produce new blood cells to improve their risk of infection and bleeding.

Official Title
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A Pilot Study of G-CSF +/- Plerixafor (AMD3100) Mobilized Donor CD34+ Enriched Peripheral Blood Mononuclear Cells for the Treatment of Allogeneic Stem Cell Transplant Recipients With Limited Donor Engraftment

Conditions
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Stem Cell Transplant Patients

Intervention / Treatment
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* Drug: G-CSF
* Drug: AMD3100
* Procedure: Leukapheresis
* Procedure: Stem Cell Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient Must be age ≥ 18 Must have ≥90 % donor cells in the unfractionated peripheral blood based on either XY FISH or standard STR. More than 60 days post allogeneic stem cell transplantation. Must meet one of the following criteria: platelets < 20,000 or ANC<500 or transfusion dependent for at least one cell line and /or on growth factor support (G-CSF) without adequate response for 30 days and no reversible etiology found after an allogeneic stem cell transplantation Patient has an ECOG performance status of 0-2. The original stem cell donor must be available, willing, and medically able to undergo Mobilization and a maximum of 2 apheresis procedures Each patient (recipient) or legal guardian and donor must be willing to participate as a research subject and must sign an informed consent form. Unrelated Donors NMDP guidelines for eligibility will be followed using G-CSF alone mobilization. Related donors Must be ≥18 yrs old and ≤ 75 years old. Donor must be sero-negative for HIV-1&2 antibody and HTLV-I&II antibody, by FDA licensed test. Donor must have adequate renal function as defined by serum creatinine ≤ 1.5X institution ULN and AST and ALT ≤ 3X ULN and total bilirubin less than 2 mg/dl. Donor must be agreeable to mobilization and the second donation of PBMC. Women of child bearing potential should be willing to avoid becoming pregnant while receiving treatment with plerixafor. Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter. Exclusion Criteria: Recipient Patients with confirmed relapse of their original disease Participation in other clinical trials that involve investigational drugs or devices except with permission from the Principal Investigator and Sponsor. Patients with documented active viral, bacterial or fungal infections. Documented allergy to murine proteins or iron dextran. Pregnancy Patients with immune mediated graft dysfunction. Donor Evidence of active infection at the time of study entry. Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy(e.g., autoimmune disease, multiple sclerosis, sickle cell trait, coronary artery disease). Pregnancy (positive serum or urine beta-HCG) or breastfeeding. Women of childbearing age must avoid becoming pregnant while on the study.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Related Donors: G-CSF & AMD3100<br>G-CSF 10 ug/kg SC daily for 5 days. AMD3100 320 mcg/kg IV over 30 min on Day 5. Leukapheresis on Day 5. | Drug: G-CSF<br>* Unrelated donors will receive only G-CSF (10 ug/Kg S/C qDay x5-6 days) prior to pheresis (collection of the stem cells). Unrelated donors will only be followed per NMDP guidelines.<br>* Other names: Neupogen;Drug: AMD3100<br> <br> * Other names: Mozobil;Procedure: Leukapheresis<br> <br> |
| Other: Recipient<br>Stem Cell Infusion on Day 0 | Procedure: Stem Cell Infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil engraftment | For recipients with ANC < 500 or growth factor support dependent at study entry, Time to neutrophil improvement is measured from the date of CD34+ selected, T-Cell depleted infusion to the first of 3 consecutive measurements of neutrophil count > 500/μl without growth factor support for >7 days prior. RBC transfusion engraftment - independence from RBCs without growth factors. | 100 days post CD34+ selected, T-Cell depleted transplant | 
| Time to platelet engraftment | For recipients with platelets < 20,000 or platelet transfusion dependent at study entry, Time to platelet improvement is measured from the date of CD34+ selected, T-Cell depleted infusion to the of 3 consecutive measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 7 days. | 100 days post CD34+ selected, T-Cell depleted transplant | 
| Time to red blood cell (RBC) improvement | For recipients who are RBC transfusion dependent at study entry, Time to RBC improvement is measured from the date of CD34+ selected, T-Cell depleted infusion to the first date of hemoglobin >9.0g/dL without > 1 RBC transfusion during the previous 56 days. | 100 days post CD34+ selected, T-Cell depleted transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the feasibility of collecting adequate donor CD34+ enriched T-cell depleted peripheral blood stem cells using G-CSF+ plerixafor from related donors and G-CSF alone from unrelated donors. |  | Day 0 (transplant day) | 
| Toxicities associated with the CD34+ collection (donors) | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. | 30 days post mobilization | 
| Phenotypically and functionally characterize donor CD34+ and donor T-cells mobilized by G-CSF from unrelated donors and mobilized with G-CSF + plerixafor from related donors. |  | Day of mobilization (Day 0) | 
| Overall survival (recipients) | Overall survival is the time from the date of CD34+ selected, T-Cell depleted infusion to death. | 1 year from date of transplant | 
| Incidence and severity of acute Graft vs Host Disease (GVHD) | Incidence and severity of acute GVHD will be assessed based on the Seattle criteria | 100 days post-transplant | 
| Toxicities associated with CD34+ cell infusion (recipients) | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. | 30 days post-transplant | 
| Disease-free survival | Disease-Free survival is the time from the date of CD34+ selected, T-Cell depleted infusion to disease relapse or death. | 1 year from date of transplant | 
| Incidence and severity of acute Graft vs Host Disease (GVHD) | Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria | 2 years post-transplant | 
| Rate of transplant-related mortality (TRM) |  | 100 days post-transplant |