Safety and Efficacy of POL6326 for Mobilization/Transplant of Sibling Donor in Patients With Hematologic Malignancies

This study is currently recruiting participants.
Verified February 2014 by Polyphor Ltd.
Sponsor:
Information provided by (Responsible Party):
Polyphor Ltd.
ClinicalTrials.gov Identifier:
NCT01413568
First received: August 5, 2011
Last updated: February 2, 2014
Last verified: February 2014
  Purpose

Determine the safety and tolerability of POL6326 when used as a single mobilization agent.


Condition Intervention Phase
Acute Myelogenous Leukemia (AML) in 1st or Subsequent Remission
Acute Lymphoblastic Leukemia (ALL) in 1st or Subsequent Remission
Chronic Myelogenous Leukemia (CML)
Non-Hodgkin's Lymphoma (NHL) or Hodgkin's Disease (HD) in 2nd or Greater Complete Remission, Partial Remission
Chronic Lymphocytic Leukemia (CLL)
Multiple Myeloma (MM)
Myelodysplastic Syndrome (MDS)
Myeloproliferative Disorder (MPD)
Drug: POL6326
Procedure: Leukapheresis
Procedure: PBSC Transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Evaluating the Safety and Efficacy of Intravenous POL6326 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Polyphor Ltd.:

Primary Outcome Measures:
  • Phase I Study - safety and tolerability of POL6326 as a mobilization agent. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Phase II Study - determine the number of allogeneic donors who require a second leukapheresis [ Time Frame: 2 days ] [ Designated as safety issue: No ]
    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:
  • Phase I Study - define maximum tolerated dose of POL6326 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Phase II Study - the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion who are safely mobilized [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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 - pharmacokinetics and pharmacodynamics of IV POL6326 [ Time Frame: Day 1-3 ] [ Designated as safety issue: No ]
    Stem cell and T-cell phenotyping

  • Phase II Study - rate of acute GVHD and chronic GVHD in patients who receive IV POL6326 mobilized peripheral blood stem cells. [ Time Frame: Day 100 (+/- 7 days) or Day 365 (+/-14 days) ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Day 365 (+/- 14 days) ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Donor (Phase I and Phase II)

On Day 1 (and possibly Day 2) POL6326 IV infusion with increasing dose levels in Phase I and with the recommended dose in Phase II

Leukapheresis collection on Day 1 (and possibly Day 2)

Drug: POL6326 Procedure: Leukapheresis
Experimental: Recipient
Day 0 - PBSC transplant with stem cells mobilized with IV POL6326
Procedure: PBSC Transplant

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Donor Inclusion Criteria

  • Donor must be 18 to 70 years of age inclusive.
  • Donor must be a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
  • Donor must have adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
  • Donor must have adequate renal function as defined by a minimum creatinine clearance (CrCl) value of >30 ml/min.
  • Donor must have adequate hepatic function as defined by a total bilirubin <3x upper limit of normal.
  • Donor must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality and no history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.
  • Donor must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed test.
  • Donor must have an ECOG performance status of 0 or 1.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Donor must demonstrate ability to be compliant with study regimen.
  • Donor must be able to understand and willing to sign an IRB approved written informed consent document.

Recipient Inclusion Criteria

  • Recipient must have available the successful collection of a POL62326 mobilized product.
  • Recipient must be 18 to 75 years of age inclusive.
  • Recipient must have a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Recipient must have one of the following diagnoses:
  • Acute myelogenous leukemia (AML) in 1st or subsequent remission
  • Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission
  • Chronic myelogenous leukemia (CML)
  • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission
  • Chronic lymphocytic leukemia (CLL)
  • Multiple myeloma (MM)
  • Myelodysplastic syndrome (MDS)
  • Myeloproliferative disorder (MPD)
  • Recipient must have adequate cardiac function with a left ventricular ejection fraction > 40%.
  • Recipient must have adequate pulmonary function defined as NO severe or symptomatic restrictive or obstructive lung disease, and formal pulmonary function testing showing an FEV1 >50% (predicted) and a DLCO >40% (predicted), corrected for hemoglobin.
  • Recipient must have adequate hepatic function as defined by a total bilirubin <3x upper limit of normal or absence of hepatic fibrosis/cirrhosis.
  • Recipient must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous CNS tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain.
  • Recipient must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed test.
  • Recipient must have an ECOG performance status of 0 or 1.
  • Recipient must demonstrate ability to be compliant with medical regimen.
  • Recipient must have life expectancy of greater than 2 months.
  • Recipient must be able to understand and willing to sign an IRB approved written informed consent document.

Donor Exclusion Criteria

  • Donor must not have an active infection at the time of study entry.
  • Donor must not have active alcohol or substance abuse within 6 months of study entry.
  • Donor must not be currently enrolled on another investigational agent study.
  • Donor must not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation.
  • Donor must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • If female and of child-bearing age, donor must not be pregnant or breastfeeding.

Recipient Exclusion Criteria

  • Recipient must not have had (the following therapies within the following timeframe):
  • Investigative drugs within 21 days
  • Recipient must have no evidence of active infection at the time of the transplant preparative regimen or at time of transplantation.
  • Recipient must have no active alcohol or substance abuse within 6 months of study entry.
  • Recipient must not be pregnant and/or breastfeeding.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01413568

Contacts
Contact: John DiPersio, M.D., Ph.D. 314-454-8304 jdipersi@dom.wustl.edu
Contact: Klaus Dembowsky, M.D., Ph.D. 0041 79 516 8763 klaus.dembowsky@polyphor.com

Locations
United States, Kansas
University of Kansas Cancer Center Not yet recruiting
Kansas City, Kansas, United States, 66205
United States, Michigan
University of Michigan Comprehensice Care Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: John DiPersio, M.D.,Ph.D.    314-454-8304    jdipersi@dom.wustl.edu   
United States, New York
Weill Cornell Medical College/NYP hospital Not yet recruiting
New York, New York, United States, 10065
Sponsors and Collaborators
Polyphor Ltd.
Investigators
Principal Investigator: John DiPersio, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Polyphor Ltd.
ClinicalTrials.gov Identifier: NCT01413568     History of Changes
Other Study ID Numbers: 201112026, POL-4
Study First Received: August 5, 2011
Last Updated: February 2, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bone Marrow Diseases
Hematologic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders

ClinicalTrials.gov processed this record on April 23, 2014