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

Myelodysplastic Syndrome (MDS) Clinical Trial

Official title:

A Pilot Study of CDX-301 (rhuFlt3L) With or Without Plerixafor for the Mobilization and Transplantation of Allogeneic Blood Cell Grafts in HLA-Matched Donor/Recipient Sibling Pairs

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02200380
• Other study ID #: CDX301-03
• Status: Terminated
• Phase: Phase 2
• First received: June 16, 2014
• Last updated: April 6, 2017
• Start date: July 2014
• Est. completion date: April 13, 2016

Study information

• Verified date: April 2017
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 36
• Est. completion date: April 13, 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Chronic Myelogenous Leukemia (CML)
• For Donors
• For Recipients
• Hodgkin Disease
• Hodgkins Disease (HD)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Non-Hodgkins Lymphoma (NHL)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Related Donors Giving Peripheral Blood Stem Cells (PBSC) to a Sibling

Intervention

Drug:
• CDX-301
Related donors will receive CDX-301 for 5 days or 7 days.
• CDX-301 and plerixafor
Related donors will receive CDX-301 for 5 or 7 days plus plerixafor.

Locations

Country	Name	City	State
United States	Emory University-Winship Cancer Institute	Atlanta	Georgia
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute	Columbus	Ohio
United States	Indiana Blood and Marrow Transplant	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	UCLA Medical Center	Los Angeles	California
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 Year
Secondary	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.	Day 6 - Day 12
Secondary	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).	Day 6 - Day 12
Secondary	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.	Day 21, Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
Secondary	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.	Day 28, Day 100, Day 180, Day 365.
Secondary	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.	Day 28, 100, 180, 365.
Secondary	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.	Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
Secondary	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.	Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
Secondary	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.	Day 21, 28, 56, 100, 180, 270, 365
Secondary	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.	Day 21, 28, 56, 100, 180, 270, 365.