Fludarabine Phosphate, Busulfan, Rabbit Anti-thymocyte Globulin, Tacrolimus, and Methotrexate in Treating Participants with Blood Cancer Undergoing Stem Cell Transplant

Status: Active

Description

This pilot early phase I trial studies how well fludarabine phosphate, busulfan, rabbit anti-thymocyte globulin, tacrolimus, and methotrexate work in treating participants with blood cancer undergoing stem cell transplant. Drugs used in chemotherapy, such as fludarabine phosphate, busulfan, and methotrexate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rabbit anti-thymocyte globulin and tacrolimus may be an effective treatment for lowering the incidence of graft-versus-host disease caused by a transplant. Giving fludarabine phosphate, busulfan, rabbit anti-thymocyte globulin, tacrolimus, and methotrexate may work better in treating participants with blood cancer.

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 of procedure (SOP)s (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 * Myelofibrosis * Lymphoma – non-Hodgkin's lymphoma (NHL) and Hodgkin’s disease * Plasma cell disorder, including myeloma, Waldenstrom’s macroglobulinemia
  • Donor availability-the patient must have an identified donor * Sibling: Availability of a 6/6 identical donor * Unrelated donor: Availability of a 6/6 unrelated 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 capability (DLCO) >= 40% predicted
  • Left ventricular ejection fraction >= 35%
  • 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: HLA 6/6 matched related or unrelated donor
  • DONOR: The donor must be healthy and must be willing to serve as a donor, based on standard 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 (if sibling donor) or by third party (i.e. NMDP) if unrelated 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 transplant (BMT)
  • History of refractory systemic infection
  • DONOR: Syngeneic donor
  • DONOR: Pregnant or lactating donor
  • DONOR: HIV or active hepatitis (Hep) B or C in the donor
  • DONOR: Donor unfit to receive granulocyte-macrophage colony-stimulating (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. To define clinical endpoints using this myeloablative allogeneic transplant regimen.

II. 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).

III. Response to treatment at 100 days.

IV. Response to treatment at one year.

V. One year survival.

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

VII. Toxicities associated with this treatment regimen.

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

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

X. To characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (VISTA, CTLA-4, PD-L1) during early immune recovery following an allogeneic stem cell transplant.

XI. Define the MDSCs frequency and checkpoint regulator expression on MDSCs, peripheral blood mononuclear cells and myeloid subsets.

OUTLINE:

Participants receive fludarabine phosphate intravenously (IV) over 30 minutes daily on days -7 to -3, busulfan IV over 3-4 hours daily on days -6 to -3, and rabbit anti-thymocyte globulin (ATG) IV over 10-12 hours on days -6 and -5. Beginning day -2, participants receive tacrolimus orally (PO) every 12 hours with taper between 90-120 days and stop by days 150-180. Participants undergo standard of care transplant on day 0. Participants then receive methotrexate on days 1, 3, and 6 or 1, 3, 6, and 11. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
Dartmouth Hitchcock Medical Center

Principal Investigator
Kenneth R. Meehan

Trial IDs

Primary ID D16127
Secondary IDs NCI-2018-01316, cphs 29619
Clinicaltrials.gov ID NCT02916979