A Safety and Tolerability Study of CDX-301 With or Without Plerixafor for Stem Cell Mobilization in Matched Related Allogeneic Donor/Recipient Sibling Transplant Pairs

Phase 2TerminatedNCT02200380

Celldex Therapeutics36 enrolled

Overview

This is an open-label, multicenter, prospective pilot study of CDX-301 with or without plerixafor as a stem cell mobilizer for allogeneic transplantation (stem cells that come from another person). HLA-matched sibling healthy volunteers (donors) and patients with protocol specified hematologic malignancies (recipients) will be enrolled.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Interventions

CDX-301DRUG

Related donors will receive CDX-301 for 5 days or 7 days.

CDX-301 and plerixaforDRUG

Related donors will receive CDX-301 for 5 or 7 days plus plerixafor.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: Donors: * Read, understood and provided written informed consent and willing to comply with all study requirements and procedures * 6 out of 6 HLA-matched sibling * Negative test for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C * Both male and female patients of childbearing potential enrolled in this trial must use adequate birth control measures * Subjects should be in generally good health and without significant medical conditions, based upon pre-study medical history, physical examination, electrocardiogram (ECG), chest X- ray, and laboratory tests * Meets all criteria to serve as a mobilized blood cell donor in accordance with all applicable individual Transplant Center criteria Recipient: * Read, understood and provided written informed consent and willing to comply with all study requirements and procedures * 6 out of 6 HLA-matched sibling * Both male and female patients of childbearing potential enrolled in this trial must use adequate birth control measures Diagnosis of one of following: * Acute Myelogenous Leukemia (AML) in 1st remission or beyond * Acute Lymphoblastic Leukemia (ALL) in 1st remission or beyond * Chronic Myelogenous Leukemia (CML) * Chronic Lymphoblastic Leukemia (CLL), relapsing after at least one prior regimen * Myelodysplastic Syndrome (MDS), either intermediate 1,2, or high risk by IPI Scoring System or transfusion dependent * Non-Hodgkins Lymphoma (NHL) or Hodgkins Disease (HD) in 2nd or greater complete remission, partial remission, or in relapse * Meets all criteria to serve as a transplant recipient in accordance with all applicable individual Transplant Center criteria Exclusion Criteria: Donors: * Unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing * Prior treatment with any rhuFlt3L product * Any vaccination within 4 weeks prior to CDX-301 dosing * Donation of blood within 8 weeks, or donation of plasma within 2 weeks prior to CDX-301 dosing * Any experimental treatment within 4 weeks prior to CDX-301 dosing * Use of systemic immunosuppressive agents (excluding topical steroids) within 12 months prior to CDX-301 dosing. * History of first degree relatives with primary or secondary immunodeficiency to include type 1 diabetes, multiple sclerosis, rheumatoid arthritis, scleroderma or psoriasis * History of tuberculosis infection * Herpes zoster within 3 months prior to starting study drug * Pregnant or nursing Recipient: * Unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing * Prior allogeneic transplant * More than one prior autologous transplant * Prior treatment with any rhuFlt3L product * Any vaccination within 4 weeks prior to transplant * Uncontrolled infection at the time of the transplant conditioning regimen * Pregnant or nursing * Any condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the study outcome

Locations (8)

UCLA Medical Center

Los Angeles, California, United States

Emory University-Winship Cancer Institute

Atlanta, Georgia, United States

Indiana Blood and Marrow Transplant

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Columbus, Ohio, United States

University of Virginia Medical Center

Charlottesville, Virginia, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Outcomes

Primary Outcomes

Safety and tolerability profile of CDX-301 with or without plerixafor in healthy adult sibling stem cell donors.

Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical examinations and adverse event reporting.

Time frame: 1 Year

Secondary Outcomes

The proportion of donors whose stem cells can be successfully mobilized and collected with a sufficient CD34+ cell count using CDX-301 with or without plerixafor as the mobilizing agent.

Donor mobilization will be considered successful if ≥ 2 million CD34+ cells/kg recipient weight are collected in no more than two leukapheresis collections.

Time frame: Day 6 - Day 12

Describe the cellular composition of allografts mobilized with CDX-301 with or without plerixafor (stem/progenitor cells, T/B/NK-cells).

To describe the cellular composition of allografts mobilized with CDX-301 with or without plerixafor (stem/progenitor cells, T/B/NK-cells).

Time frame: Day 6 - Day 12

Incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor

To determine the incidence of and kinetics of neutrophil, and platelet recovery after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 21, Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.

Incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with CDX301-03 with or without plerixafor.

To determine the incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 28, Day 100, Day 180, Day 365.

Rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

To assess the rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 28, 100, 180, 365.

Incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

To determine the incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.

Incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor in transplant recipients.

To determine the incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor in transplant recipients.

Time frame: Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.

Number of post-transplant days of hospitalization in patients that received hematopoietic cells mobilized with CDX-301 with or without plerixafor.

To determine the number of post transplant days of hospitalization after receiving hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 21, 28, 56, 100, 180, 270, 365

Incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

To determine the incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.

Time frame: Day 21, 28, 56, 100, 180, 270, 365.