Cyclophosphamide, Fludarabine Phosphate, and Total Body Radiation, before Donor Stem Cell Transplant in Treating Participants with Blood Disorders and Blood Cancers

Status: Active

Description

This phase III trial studies how well cyclophosphamide, fludarabine phosphate, and total body radiation before donor stem cell transplant work in treating participants with blood disorders and blood cancers. Giving chemotherapy such as cyclophosphamide and fludarabine phosphate and total body radiation before a stem cell transplant helps stop the growth of cells in the bone marrow. When the healthy cells from a donor are infused into the participant, they may help the patient's bone marrow make stem cells, red blood cells, and platelets. The donated cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Eligibility Criteria

Inclusion Criteria

  • 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 procedures (SOPs) (DHMC SOP – Pre-transplant Evaluation of Allogeneic Recipient).
  • 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 (AML), acute lymphoblastic leukemia (ALL) * Chronic leukemia – Chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL) * Myelodysplasia * Myeloproliferative disorder * Myelofibrosis * Lymphoma – Non-Hodgkin lymphoma (NHL) or Hodgkin’s disease * Plasma cell disorder, including myeloma, Waldenstrom’s macroglobulinemia.
  • The patient must have an identified RELATED haploidentical (haplo)-identical donor.
  • No human immunodeficiency virus (HIV) infection or active hepatitis B or C.
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2.
  • Carbon monoxide diffusing capacity (DLCO) 40% predicted.
  • Left ventricular ejection fraction >= 40%.
  • Serum bilirubin < 2 x upper limit of normal.
  • Transaminases < 3 x 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 principal investigator [PI] can make a decision).
  • DONOR: Human leukocyte antigen (HLA) haplo-identical matched related.
  • DONOR: 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.
  • DONOR: The donor must have no significant co-morbidities that would put the donor at marked increased risk.
  • DONOR: There is no age restriction for the donor.
  • DONOR: Informed consent must be signed by donor.

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 transplantation (BMT).
  • History of refractory systemic infection.
  • DONOR: The NMDP guidelines for exclusion criteria will be used.
  • DONOR: Pregnant or lactating donor.
  • DONOR: HIV or active hepatitis (Hep) B or C in the donor.
  • DONOR: Donor unfit to receive granulocyte colony-stimulating factor (G-CSF) and undergo apheresis.
  • DONOR: A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible.

Locations & Contacts

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Kenneth R. Meehan
Phone: 603-650-4628

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To define the 100-day survival of patients being treated on this regimen.

SECONDARY OBJECTIVES:

I. Time to marrow engraftment (defined as absolute neutrophil count > 500/mm^3 and platelets > 20,000/mcl for three consecutive days (count first day as engraftment).

II. Response to treatment at 100 days.

III. Response to treatment at one year.

IV. One year survival.

V. Treatment-related mortality in the first 100 days.

VI. Toxicities associated with this treatment regimen.

VII. Incidence of acute and chronic graft versus host disease (GVHD).

VIII. Donor-recipient chimerism following transplant at days 30, 60 and 90.

IX: To characterize the incidence, prevalence and function of immune checkpoint regulators (VISTA, CTLA-4, PD-1) during early immune recovery following an allogeneic stem cell transplant.

EXPLORATORY OBJECTIVES:

I. In those patients experiencing GVHD, will define the myeloid-derived suppressor cells (MDSCs) frequency and checkpoint regulator expression on MDSCs, peripheral blood mononuclear cells and myeloid subsets.

OUTLINE:

Participants receive cyclophosphamide intravenously (IV) over 30 minutes on days -6 and -5, fludarabine phosphate IV over 30 minutes on days -6 to -2, and undergo total body radiation once on day -1. Participants undergo allogeneic hematopoietic stem cell transplant on day 0. Participants then receive cyclophosphamide IV over 90 minutes on days 3-4, tacrolimus orally (PO) or IV daily on days 5-180, and mycophenolate mofetil PO thrice daily (TID) on days 5-35 days after transplant for about 35 days. Participants also receive filgrastim subcutaneously (SC) on day 5 until absolute neutrophil count (ANC) > 1000/mcL for 3 days.

After completion of study treatment, participants are followed up for 30 days, weekly for 3 months, and then monthly for 1 year.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Dartmouth Hitchcock Medical Center

Principal Investigator
Kenneth R. Meehan

Trial IDs

Primary ID D17170
Secondary IDs NCI-2018-01157, cphs 30703
Clinicaltrials.gov ID NCT03480360