Clinical Trial Finder

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

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.

Arms

Other: 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

Interventions

Drug: - Cyclophosphamide

14.5 mg/kg for 2 days (days -6, -5) and then 50 mg/kg for two days (days 3, 4)

Drug: - Fludarabine

30 mg/m2 daily for 5 days

Radiation: - Total Body Irradiation

200 centigray (cGy) for one day (day -1)

Drug: - Tacrolimus

1 mg IV daily, (or the oral equivalent) adjusted to achieve a level between 5 and 15 ng/ml. If there is no evidence of GVHD, discontinue Tacrolimus by Day 180.

Drug: - cellcept

dose at 15 mg/kg po three times per day (maximum dose of 3 grams/day). Stop Cellcept at Day 35 following transplantation.

Drug: - g-csf

5 mcg/kg/d starting day 5 and continue until Absolute Neutrophil Count (ANC) > 1000/mcL for 3 days.

Procedure: - Peripheral Blood Transplant

cell dose goal: < 5 x 106 Hematopoietic progenitor cell antigen CD34+ cells/kg recipient weight