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
Primary Purpose
For Donors, Related Donors Giving Peripheral Blood Stem Cells (PBSC) to a Sibling, For Recipients
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CDX-301
CDX-301 and plerixafor
Sponsored by
About this trial
This is an interventional treatment trial for For Donors
Eligibility Criteria
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
Sites / Locations
- UCLA Medical Center
- Emory University-Winship Cancer Institute
- Indiana Blood and Marrow Transplant
- University of Iowa
- Wake Forest Baptist Health
- Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
- University of Virginia Medical Center
- Virginia Commonwealth University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
CDX-301
CDX-301 and plerixafor
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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).
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02200380
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Study Start Date
July 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
April 13, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celldex Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
For Donors, Related Donors Giving Peripheral Blood Stem Cells (PBSC) to a Sibling, For Recipients, Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Myelodysplastic Syndrome (MDS), Chronic Myelogenous Leukemia (CML), Non-Hodgkins Lymphoma (NHL), Hodgkins Disease (HD), Chronic Lymphocytic Leukemia (CLL)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CDX-301
Arm Type
Experimental
Arm Title
CDX-301 and plerixafor
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CDX-301
Intervention Description
Related donors will receive CDX-301 for 5 days or 7 days.
Intervention Type
Drug
Intervention Name(s)
CDX-301 and plerixafor
Intervention Description
Related donors will receive CDX-301 for 5 or 7 days plus plerixafor.
Primary Outcome Measure Information:
Title
Safety and tolerability profile of CDX-301 with or without plerixafor in healthy adult sibling stem cell donors.
Description
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 Outcome Measure Information:
Title
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.
Description
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
Title
Describe the cellular composition of allografts mobilized with CDX-301 with or without plerixafor (stem/progenitor cells, T/B/NK-cells).
Description
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
Title
Incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor
Description
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.
Title
Incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with CDX301-03 with or without plerixafor.
Description
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.
Title
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.
Description
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.
Title
Incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.
Description
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.
Title
Incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor in transplant recipients.
Description
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.
Title
Number of post-transplant days of hospitalization in patients that received hematopoietic cells mobilized with CDX-301 with or without plerixafor.
Description
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
Title
Incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.
Description
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Emory University-Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana Blood and Marrow Transplant
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Virginia Medical Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Virginia Commonwealth University Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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