Clinical Trial 18814

Cancer Type: Malignant Hematology
Interventions:busulfan; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Farhad Khimani

Overview

Study Title

A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Patients with Hematologic Malignancies

Summary

The purpose of this study is to see if using a mismatched unrelated donor (MMUD) is safe and effective in participants undergoing bone marrow transplant.

Objective

The primary objective is to determine OS through 1 year after HLA MMUD bone marrow HCT using PTCy. Secondary objectives include estimating the following: PFS at Day+180 and 1 year post-HCT; TRM at Day+100, Day+180, and 1 year post-HCT; cumulative incidence of neutrophil recovery; cumulative incidence of platelet recovery; cumulative incidence of primary graft failure; donor chimerism; cumulative incidences of aGVHD and cGVHD; cumulative incidences of viral reactivations and infections; cumulative incidence of relapse/progression; and cumulative incidences of TMA and VOD/SOS. The proportion of subjects proceeding to HCT after informed consent will be described. The donor selection characteristics will also be described. Time to donor identification from the search request will be described. Incidence of development of donor clonal hematopoiesis will be described. Analysis of long-term survivors will be performed for subjects who consent to the CIBMTR Research Database protocol using routine data collection forms and time points per CIBMTR requirements.

Inclusion Criteria

  • Age ≥ 15 years and less than 71 years at the time of signing the informed consent form
  • Partially HLA-mismatched unrelated donor: HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of 4/8 at HLA-A, -B, -C, and -DRB1 is required
  • Product planned for infusion is bone marrow
  • Disease and disease status: (a) Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma; acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute undifferentiated leukemia (AUL); (b) Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with de novo MDS who have or have previously had Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is not a requirement; Subjects must have > Performance status: Karnofsky or Lansky score ≥ 60%
  • Adequate organ function
  • Participants ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements. Legal guardian permission must be obtained for participants less than 18 years of age. Pediatric participants will be included in age appropriate discussion in order to obtain assent.
  • Potential participants with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a hematologic malignancy who meets all other eligibility requirements must: (a) Receive only RIC regimen (i.e., Regimen A); (b) Be willing to comply with effective antiretroviral therapy (ARV); (c) Have achieved a sustained virologic response for 12 weeks after cessation of hepatitis C antiviral treatment (in HIV-positive patients with hepatitis C).

  • Exclusion Criteria

  • HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor available. This exclusion does not apply to HIV-positive potential participants who have a CCR5delta32 homozygous donor.
  • Autologous HCT less than 3 months prior to the time of signing the informed consent form
  • Females who are breast-feeding or pregnant
  • HIV-positive: (a) Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may pose an excessive risk for transplantation-related morbidity as determined by the Treatment Review Committee;(b) Untreatable HIV infection due to multidrug ARV resistance. Potential participants with a detectable or standard viral load > 750 copies/mL should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the ARV review; (c) May not be currently prescribed ritonavir, cobacistat and/or zidovudine.
  • Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
  • Prior allogeneic HCT
  • History of primary idiopathic myelofibrosis
  • MDS participants may not receive RIC and must be less than 50 years of age at the time of signing the informed consent form
  • May not be eligible for inclusion in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1101 protocol