Safety and Efficacy of POL6326 for Mobilization/Transplant of Sibling Donor in Patients With Hematologic Malignancies
- Conditions
- Acute Myeloid Leukemia in RemissionAdult Acute Lymphoblastic Leukemia in RemissionChronic Myelogenous Leukemia (CML)Non-Hodgkin's Lymphoma (NHL) or Hodgkin's Disease (HD) in 2nd or Greater Complete Remission, Partial RemissionChronic Lymphocytic Leukemia (CLL)Multiple Myeloma (MM)Myelodysplastic Syndrome (MDS)Myeloproliferative Disorders
- Interventions
- Registration Number
- NCT01413568
- Lead Sponsor
- Polyphor Ltd.
- Brief Summary
Determine the safety and tolerability of POL6326 when used as a single mobilization agent.
- Detailed Description
Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling donors. This process requires from four to six days of G-CSF injection and is associated with significant morbidity, most notably bone pain. POL6326 is associated with few side effects and collection of cells occurs on the same day as POL6326 administration.
This study will evaluate the safety and efficacy of this novel agent for hematopoietic progenitor cell mobilization and allogeneic transplantation based on the following hypotheses:
1. Donors mobilized with intravenous POL6326 will require fewer collections than have previously been seen for donors mobilized with subcutaneous plerixafor.
2. Healthy HLA-matched donors receiving one or two infusions of POL6326 will mobilize sufficient CD34+ cells (at least 2.0 x 106 CD34+ cells/kg recipient weights) following leukapheresis to support a hematopoietic cell transplant.
3. IV POL6326 will result in more rapid kinetics and a higher maximum (peak) of human CD34+ stem cells mobilized from human normal allogeneic donors compared to previous donors who were mobilized with plerixafor.
4. The hematopoietic cells mobilized by IV POL6326 will be functional and will result in prompt and durable hematopoietic engraftment following transplantation into HLA-identical siblings with advanced hematological malignancies using various non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD prophylaxis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Donor (Phase I and Phase II) POL6326 On Day 1 (and possibly Day 2) POL6326 IV Infusion with increasing dose levels in Phase I or with random dose assignment (from the 2 selected from Phase I) in phase II Leukapheresis collection on Day 1 (and possibly Day 2) Donor (Phase I and Phase II) Leukapheresis On Day 1 (and possibly Day 2) POL6326 IV Infusion with increasing dose levels in Phase I or with random dose assignment (from the 2 selected from Phase I) in phase II Leukapheresis collection on Day 1 (and possibly Day 2) Recipient PBSC Transplant Day 0 - PBSC transplant with stem cells mobilized with IV POL6326
- Primary Outcome Measures
Name Time Method Phase I Study - safety and tolerability of POL6326 as a mobilization agent. 30 days Phase II Study - determine the number of allogeneic donors who require a second leukapheresis 2 days Determine the number of allogeneic donors which collect \>= 2 mill CD34+ cells with one or two leukapheresis procedures treated with IV POL6326. Comparison with historic group of donors who were mobilized with 240 µg/kg SC plerixafor.
- Secondary Outcome Measures
Name Time Method Phase I Study - define maximum tolerated dose of POL6326 30 days Phase II Study - pharmacokinetics and pharmacodynamics of IV POL6326 Day 1-3 Stem cell and T-cell phenotyping
Phase II Study - the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion who are safely mobilized 30 days To estimate the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion from whom \> 2 mill CD34+ cells/kg recipient weight are safely mobilized following one or two leukapheresis procedures
Phase II Study - rate of acute GVHD and chronic GVHD in patients who receive IV POL6326 mobilized peripheral blood stem cells. Day 100 (+/- 7 days) or Day 365 (+/-14 days) Acute GVHD - Day 100 (+/- 7 days) Chronic GVHD - Day 365 (+/- 14 days)
Phase II Study - kinetics of neutrophil and platelet engraftment in recipients of POL6326 mobilized peripheral blood stem cells. Day 365 (+/- 14 days)
Trial Locations
- Locations (2)
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States