Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression

Dartmouth Health

Status and phase

Active, not recruiting

Phase 3

Conditions

Myelofibrosis

Plasma Cell Disorder

Myelodysplasia

Chronic Myeloid Leukemia

Lymphoma

Chronic Lymphocytic Leukemia

Lymphoma, Non-Hodgkin

Acute Myeloid Leukemia

Myeloproliferative Disorder

Treatments

Drug: Cyclophosphamide

Drug: cellcept

Radiation: Total Body Irradiation

Procedure: Peripheral Blood Transplant

Drug: Fludarabine

Drug: Tacrolimus

Drug: g-csf

Study type

Interventional

Funder types

Other

Identifiers

NCT03480360

D17170

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

21 participants in 1 patient group

Johns Hopkins' conditioning regimen

Other group

Description:

Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant

Treatment: