Clinical trial NCT03480360: Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression
Official title: Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates Examining Checkpoint Immune Regulators' Expression
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Myelodysplasia
Myeloproliferative Disorder
Myelofibrosis
Lymphoma
Lymphoma, Non-Hodgkin
Plasma Cell Disorder
Keywords: haploidentical
transplant
peripheral blood
allogeneic
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* Donor availability- the patient must have an identified RELATED haplo-identical donor
* No Human Immunodeficiency Virus infection or active hepatitis B or C
* Eastern Cooperative Oncology Group performance status: 0-2
* Diffusing capacity of carbon monoxide (DLCO) greater than or equal to 40 % predicted
* Left ventricular ejection fraction greater than or equal to 40%
* Serum bilirubin \< 2x upper limit of normal; transaminases \< 3x normal at the time of transplant
* No active or uncontrollable infection
* In female, a negative pregnancy test if experiencing menstrual periods
* No major organ dysfunction precluding transplantation
* No evidence of an active malignancy that would limit the patient's survival to less than 2 years. (If there is any question, the PI can make a decision).

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

* The NMDP guidelines for exclusion criteria will be used (Appendix). In addition, the following donors are NOT eligible:
* Pregnant or lactating donor
* HIV or active Hep B or C in the donor
* Donor unfit to receive G-CSF and undergo apheresis
* A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible

Primary outcomes:
measure: Number of Participants Who Survived to 100-Days Post-transplant
timeFrame: 100 days post date of peripheral blood transplant
measure: Number of Participants Who Survived to One Year Post-Transplant.
timeFrame: One year post date of peripheral blood transplant
measure: Number of Participants Who Experienced a Successful Engraftment
timeFrame: Post-peripheral blood transplant
measure: Number of Participants Who Achieved a Response to Treatment at 100 Days
timeFrame: 100 days post-peripheral blood transplant
measure: Number of Participants Who Achieved a Response to Treatment at One Year
timeFrame: One year post-peripheral blood transplant
measure: Number of Participants Who Experienced Toxicities Associated With This Treatment Regimen
timeFrame: Post-peripheral blood transplant
measure: Number of Participants Who Had Incidence of Acute GVHD
timeFrame: Post-peripheral blood transplant
measure: Number of Participants Who Had Incidence of Chronic GVHD
timeFrame: Post-peripheral blood transplant
measure: Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
timeFrame: Days 30, 60, and 90 post-peripheral blood transplant
measure: Number of Participants Who Experienced Treatment-Related Mortality Within the First 100 Days
timeFrame: 100 days post-peripheral blood transplant
Secondary outcomes:
measure: Immune Checkpoint Regulators - Incidence
timeFrame: Days 30, 60, and 90 post-transplant
measure: Myeloid-derived Suppressor Cells (MDSCs) After Graft vs. Host Disease (GVHD) Diagnosis - Checkpoint Regulator Expression
timeFrame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
measure: MDSCs After GVHD Diagnosis - Peripheral Blood Mononuclear Cells
timeFrame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
measure: MDSCs After GVHD Diagnosis - Myeloid Subsets Using Flow Cytometry
timeFrame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
measure: MDSCs After GVHD Diagnosis - Frequency
timeFrame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
measure: Immune Checkpoint Regulators - Prevalence
timeFrame: Days 30, 60, and 90 post-transplant
measure: Immune Checkpoint Regulators - Function
timeFrame: Days 30, 60, and 90 post-transplant
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Kenneth Meehan, MD
role: PRINCIPAL_INVESTIGATOR
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