Reduced Intensity Flu/Mel/TBI Conditioning for HAPLO HCT Patients With Hematologic Malignancies

Overview

This is a single arm, phase II trial of HLA-haploidentical related hematopoietic cells transplant (Haplo-HCT) using reduced intensity conditioning (fludarabine and melphalan and total body irradiation). Peripheral blood is the donor graft source. This study is designed to estimate disease-free survival (DFS) at 18 months post-transplant.

Full Title of Study: “Reduced-Intensity Fludarabine, Melphalan, and Total Body Irradiation Conditioning for Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2022

Interventions

  • Drug: Fludarabine
    • Fludarabine 30mg/m^2/day will be administered over 30-60 minutes intravenous infusion on Days -6 through -2 for a total dose of 150 mg/m^2
  • Drug: Melphalan
    • Melphalan 70 mg/m^2 over 45 minutes will be administered Day -6. Melphalan dose will be calculated based on Actual Body Weight.
  • Radiation: Total Body Irradiation
    • Total Body Irradiation (TBI) will be delivered at a dose of 200 centigray units (cGy)

Arms, Groups and Cohorts

  • Experimental: Conditioning Regimen + Transplant
    • All participants will receive a conditioning regimen of Fludarabine, Melphalan and Total Body Irradiation prior to transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT)

Clinical Trial Outcome Measures

Primary Measures

  • Disease Free Survival
    • Time Frame: Up to 18 months post-transplant
    • Disease Free Survival (DFS) is defined as the time from the date of Peripheral Blood Stem Cell Transplant (PBSCT) to first documentation of relapse or death due to any cause, whichever comes first.

Secondary Measures

  • Graft vs Host Disease (GVHD) free survival
    • Time Frame: At 180 days post-transplant
    • GVHD-free survival is defined as the time from the date of PBSCT to date of events which include grade III-IV acute GVHD and systemic therapy-requiring chronic GVHD.
  • Overall Survival (OS)
    • Time Frame: Up to 18 months
    • OS is defined as the time from the date of PBSCT to the date of death due to any cause.
  • Treatment Related Mortality (TRM) at 6 months
    • Time Frame: at 6 months post-transplant
    • TRM is defined as death not directly due to disease
  • Treatment Related Mortality (TRM) at 18 months
    • Time Frame: at 18 months post-transplant
    • TRM is defined as death not directly due to disease
  • Relapse Free Survival (RFS)
    • Time Frame: Up to 18 months post-transplant
    • RFS is defined as the time from the date of PBSCT to relapse or death.

Participating in This Clinical Trial

Inclusion Criteria

  • Age ≥ 55 years or HCT Co-Morbidity score (HCT-CI) >/=3
  • Lack of a suitable 8/8 HLA-matched sibling donor
  • Adequate performance status is defined as Karnofsky score ≥ 70%
  • Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors must be HLA-haploidentical relatives including, but not limited to, children, siblings, or parents, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.
  • Acute Myeloid Leukemia (AML): Must be in remission with morphology (<5% blasts)
  • Acute Lymphoblastic Leukemia (ALL)/lymphoma second or greater complete remission (CR) first CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities, first CR high-risk ALL
  • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
  • Myelodysplastic syndrome: any subtype including refractory anemia (RA) if severe pancytopenia or complex cytogenetics. Blasts must be less than 5%. If 5% of more requires chemotherapy for cytoreduction to </=5% prior to transplantation.
  • Chronic Myelogenous leukemia in accelerated phase: patient must have failed at least two different Tyrosine Kinase Inhibitor (TKI)s, been intolerant to all TKIs, or have T315l mutation
  • Myeloproliferative neoplasms/myelofibrosis: Blasts must be less than 5%. If 5% or more requires chemotherapy for cytoreduction to </=5% prior to transplantation
  • Relapsed large-cell lymphoma, mantle-cell lymphoma or Hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
  • Burkitt's lymphoma in second CR or subsequent CR
  • Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/Partial Response (PR) that has failed or ineligible for an autologous transplant
  • Natural killer cell malignancies
  • Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting up to 12 months are eligible after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
  • Lymphoplasmacytic lymphoma is eligible after initial therapy if chemotherapy sensitive
  • Adequate organ function as defined per protocol
  • Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use adequate birth control during study treatment

Exclusion Criteria

  • Pregnant or breastfeeding
  • Untreated active infection
  • Active HIV infection
  • Prior allogenic transplant at any time prior or less than 6 months since prior autologous transplant (if applicable)
  • Active central nervous system malignancy
  • Favorable risk AML defined as per protocol

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • H. Lee Moffitt Cancer Center and Research Institute
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Hany Elmariah, MD, MS, Principal Investigator, Moffitt Cancer Center

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