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

Brief Title

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

Official Title

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

Brief Summary

      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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Disease Free Survival

Secondary Outcome

 Graft vs Host Disease (GVHD) free survival

Condition

Acute Myeloid Leukemia

Intervention

Fludarabine

Study Arms / Comparison Groups

 Conditioning Regimen + Transplant

Description:  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)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

December 6, 2019

Completion Date

February 2025

Primary Completion Date

February 11, 2024

Eligibility Criteria

        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  12 months are eligible after at least two prior
             therapies

          -  Patients with primary, refractory disease. Bulky disease and an estimated tumor
             doubling time of less than one month require debulking therapy prior to transplant.

          -  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

          -  Active central nervous system malignancy

          -  Favorable risk AML defined as having one of the following:

          -  t(8,21) without cKIT mutation or evidence of immunophenotypic, cytogenetic or
             molecular minimal residual disease (MRD)

          -  inv(16) or t(16;16) without cKIT mutation or evidence of MRD

          -  Normal karyotype with mutated NPM1 but FLT3-ITD wild type without evidence of MRD

          -  Normal karyatype with double mutated CEBPA without evidence of MRD

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Hany Elmariah, MD, MS, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT04191187

Organization ID

MCC-20131

Responsible Party

Sponsor

Study Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Study Sponsor

Hany Elmariah, MD, MS, Principal Investigator, Moffitt Cancer Center

Verification Date

January 2023