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)
Conditions
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.
Interventions
DRUGCDX-301
Related donors will receive CDX-301 for 5 days or 7 days.
DRUGCDX-301 and plerixafor
Related donors will receive CDX-301 for 5 or 7 days plus plerixafor.
Sponsors
Celldex Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability profile of CDX-301 with or without plerixafor in healthy adult sibling stem cell donors. | 1 Year | Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical examinations and adverse event reporting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | Day 21, Day 28, Day 56, Day 100, Day 180, Day 270, Day 365. | 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. | Day 28, Day 100, Day 180, Day 365. | 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. | Day 28, 100, 180, 365. | 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. |
| 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. | Day 6 - Day 12 | Donor mobilization will be considered successful if ≥ 2 million CD34+ cells/kg recipient weight are collected in no more than two leukapheresis collections. |
| 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. | 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. | Day 21, 28, 56, 100, 180, 270, 365 | 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. | Day 21, 28, 56, 100, 180, 270, 365. | 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. |
| 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. | 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. |
Countries
United States
Outcome results
None listed