Clinical trial NCT01026987: Granulocyte Colony-stimulating Factor (G-CSF) Plus or Minus AMD3100 for Engraftment Post Allogeneic Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Stem Cell Transplant Patients
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2009-12-07
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to neutrophil engraftment
timeFrame: 100 days post CD34+ selected, T-Cell depleted transplant
measure: Time to platelet engraftment
timeFrame: 100 days post CD34+ selected, T-Cell depleted transplant
measure: Time to red blood cell (RBC) improvement
timeFrame: 100 days post CD34+ selected, T-Cell depleted transplant
Secondary outcomes:
measure: 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.
timeFrame: Day 0 (transplant day)
measure: Toxicities associated with the CD34+ collection (donors)
timeFrame: 30 days post mobilization
measure: 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.
timeFrame: Day of mobilization (Day 0)
measure: Overall survival (recipients)
timeFrame: 1 year from date of transplant
measure: Incidence and severity of acute Graft vs Host Disease (GVHD)
timeFrame: 100 days post-transplant
measure: Toxicities associated with CD34+ cell infusion (recipients)
timeFrame: 30 days post-transplant
measure: Disease-free survival
timeFrame: 1 year from date of transplant
measure: Incidence and severity of acute Graft vs Host Disease (GVHD)
timeFrame: 2 years post-transplant
measure: Rate of transplant-related mortality (TRM)
timeFrame: 100 days post-transplant
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: John DiPersio, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: