Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates Examining Checkpoint Immune Regulators' Expression
Overview
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
Overview
Brief Summary
The standard Johns Hopkins' regimen will be used in study subjects, with the use of donor peripheral blood stem cells, rather than marrow. Clinical outcomes will be defined while focusing efforts on immune reconstitution focusing on immune checkpoint regulators after a related haploidentical stem cell transplant.
Detailed Description
We propose a clinical trial to define clinical endpoints, including engraftment, 100-day survival and one year survival (Objective #1). We will characterize the incidence, prevalence and function of immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). We will correlate these laboratory results with clinical outcomes and the incidence of GVHD. As an exploratory aim, in those patients experiencing GVHD and requiring treatment, we will define the frequency/expression of checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age: less than 75 years
- •The patient must be approved for transplant by the treating transplant physician. This includes completion of their pre-transplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedure (SOP) (DHMC SOP - Pre-transplant Evaluation of allogeneic recipient (Appendix).
- •The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
- •Acute leukemia - Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
- •Chronic leukemia - Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia
- •Myelodysplasia
- •Myeloproliferative disorder
- •Myelofibrosis
- •Lymphoma - Non-Hodgkin's Lymphoma or Hodgkin's disease
- •Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
Exclusion Criteria
- •Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- •Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- •History of refractory systemic infection
- •DONOR ELIGIBILITY
- •Human leukocyte antigen (HLA) haplo-identical matched related.
- •The donor must be healthy and must be willing to serve as a donor, based on standard National Marrow Donor Program (NMDP) guidelines and DHMC SOP - Donor Evaluation (Appendix)
- •The donor must have no significant co-morbidities that would put the donor at marked increased risk
- •There is no age restriction for the donor
- •Informed consent must be signed by donor
- •DONOR EXCLUSION CRITERIA
Arms & Interventions
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: Cyclophosphamide (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: Fludarabine (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: Total Body Irradiation (Radiation)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: Tacrolimus (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: cellcept (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: g-csf (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
Intervention: Peripheral Blood Transplant (Procedure)
Outcomes
Primary Outcomes
Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
Time Frame: Days 30, 60, and 90 post-peripheral blood transplant
Define subjects who experience donor-recipient chimerism following transplant at days 30, 60 and 90. All patients were assessed for donor-recipient chimerism at days 30, 60, and 90, but only one patient experienced chimerism. Day 90 for this patient is reported.
Number of Participants Who Survived to 100-Days Post-transplant
Time Frame: 100 days post date of peripheral blood transplant
Define 100-day survival of subjects
Number of Participants Who Survived to One Year Post-Transplant.
Time Frame: One year post date of peripheral blood transplant
Define one year survival of subjects
Number of Participants Who Experienced a Successful Engraftment
Time Frame: Post-peripheral blood transplant
Define number of subjects who experience a successful engraftment: Defined as absolute neutrophil count \> 500/mm3 and platelets \> 20,000/mcl for three consecutive days (count first day as engraftment)
Number of Participants Who Achieved a Response to Treatment at 100 Days
Time Frame: 100 days post-peripheral blood transplant
Define response to treatment at 100 days post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Number of Participants Who Achieved a Response to Treatment at One Year
Time Frame: One year post-peripheral blood transplant
Define response to treatment at one year post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Number of Participants Who Experienced Toxicities Associated With This Treatment Regimen
Time Frame: Post-peripheral blood transplant
Define subjects who experienced toxicities associated with this treatment regimen
Number of Participants Who Had Incidence of Acute GVHD
Time Frame: Post-peripheral blood transplant
Define subjects who had incidence of acute GVHD
Number of Participants Who Had Incidence of Chronic GVHD
Time Frame: Post-peripheral blood transplant
Define subjects who had incidence of chronic GVHD
Number of Participants Who Experienced Treatment-Related Mortality Within the First 100 Days
Time Frame: 100 days post-peripheral blood transplant
Define subjects who experienced treatment-related mortality within the first 100 days post-peripheral blood transplant
Secondary Outcomes
- Myeloid-derived Suppressor Cells (MDSCs) After Graft vs. Host Disease (GVHD) Diagnosis - Checkpoint Regulator Expression(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- MDSCs After GVHD Diagnosis - Frequency(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- Immune Checkpoint Regulators - Incidence(Days 30, 60, and 90 post-transplant)
- MDSCs After GVHD Diagnosis - Peripheral Blood Mononuclear Cells(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- MDSCs After GVHD Diagnosis - Myeloid Subsets Using Flow Cytometry(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- Immune Checkpoint Regulators - Function(Days 30, 60, and 90 post-transplant)
- Immune Checkpoint Regulators - Prevalence(Days 30, 60, and 90 post-transplant)
Investigators
Kenneth Meehan
Principal Investogator- Kenneth Meehan, MD Staff Physician
Dartmouth-Hitchcock Medical Center