Clinical trial NCT02200380: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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)
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-07-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and tolerability profile of CDX-301 with or without plerixafor in healthy adult sibling stem cell donors.
timeFrame: 1 Year
Secondary outcomes:
measure: 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.
timeFrame: Day 6 - Day 12
measure: Describe the cellular composition of allografts mobilized with CDX-301 with or without plerixafor (stem/progenitor cells, T/B/NK-cells).
timeFrame: Day 6 - Day 12
measure: Incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor
timeFrame: Day 21, Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
measure: Incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with CDX301-03 with or without plerixafor.
timeFrame: Day 28, Day 100, Day 180, Day 365.
measure: 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.
timeFrame: Day 28, 100, 180, 365.
measure: Incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.
timeFrame: Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
measure: Incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor in transplant recipients.
timeFrame: Day 28, Day 56, Day 100, Day 180, Day 270, Day 365.
measure: Number of post-transplant days of hospitalization in patients that received hematopoietic cells mobilized with CDX-301 with or without plerixafor.
timeFrame: Day 21, 28, 56, 100, 180, 270, 365
measure: Incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with CDX-301 with or without plerixafor.
timeFrame: Day 21, 28, 56, 100, 180, 270, 365.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University-Winship Cancer Institute
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplant
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
Study officials:
References: