Granulocyte Colony-stimulating Factor (G-CSF) Plus or Minus AMD3100 for Engraftment Post Allogeneic Transplant
- Conditions
- Stem Cell Transplant Patients
- Interventions
- Registration Number
- NCT01026987
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Related Donors: G-CSF & AMD3100 AMD3100 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. Related Donors: G-CSF & AMD3100 Leukapheresis 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. Recipient Stem Cell Infusion Stem Cell Infusion on Day 0 Related Donors: G-CSF & AMD3100 G-CSF 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.
- Primary Outcome Measures
Name Time Method Time to neutrophil engraftment 100 days post CD34+ selected, T-Cell depleted transplant 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.Time to platelet engraftment 100 days post CD34+ selected, T-Cell depleted transplant 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.
Time to red blood cell (RBC) improvement 100 days post CD34+ selected, T-Cell depleted transplant 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.
- Secondary Outcome Measures
Name Time Method Overall survival (recipients) 1 year from date of transplant Overall survival is the time from the date of CD34+ selected, T-Cell depleted infusion to death.
Incidence and severity of acute Graft vs Host Disease (GVHD) 2 years post-transplant Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria
Toxicities associated with CD34+ cell infusion (recipients) 30 days post-transplant NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
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) Disease-free survival 1 year from date of transplant Disease-Free survival is the time from the date of CD34+ selected, T-Cell depleted infusion to disease relapse or death.
Rate of transplant-related mortality (TRM) 100 days post-transplant Toxicities associated with the CD34+ collection (donors) 30 days post mobilization NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
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)
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States