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

NCT04191187 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MCC-20131
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Relapsed Chronic Lymphocytic Leukemia; Biphenotypic Acute Leukemia; Undifferentiated Leukemia; Prolymphocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia; Myeloproliferative Neoplasm; Relapsed Large Cell Lymphoma; Mantle Cell Lymphoma; Hodgkin Lymphoma; Burkitt Lymphoma; Relapsed T-Cell Lymphoma; Relapsed Small Lymphocytic Lymphoma; Relapsed Marginal B-cell Lymphoma; Relapsed Follicular Lymphoma; Lymphoplasmacytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  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.

  Up to 18 months post-transplant

Secondary Outcomes (5)

• Percentage of Participants With Graft vs Host Disease (GVHD) Free Survival

  At 180 days post-transplant

• Percentage of Participants Overall Survival (OS)

  Up to 18 months

• Percentage of Participants With Treatment Related Mortality (TRM) at 6 Months

  at 6 months post-transplant

• Percentage of Participants With Treatment Related Mortality (TRM) at 18 Months

  at 18 months post-transplant

• Percentage of Participants With Relapse Free Survival (RFS)

  Up to 18 months post-transplant

Study Arms (1)

Conditioning Regimen + Transplant

EXPERIMENTAL

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)

Drug: Fludarabine; Drug: Melphalan; Radiation: Total Body Irradiation

Interventions

Total Body Irradiation RADIATION

Total Body Irradiation (TBI) will be delivered at a dose of 200 centigray units (cGy)

Conditioning Regimen + Transplant

Fludarabine DRUG

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

Also known as: Fludara

Conditioning Regimen + Transplant

Melphalan DRUG

Melphalan 70 mg/m\^2 over 45 minutes will be administered Day -6. Melphalan dose will be calculated based on Actual Body Weight.

Also known as: Alkeran

Conditioning Regimen + Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 with any of the following:

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Leukemia, Prolymphocytic; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Mantle-Cell; Hodgkin Disease; Burkitt Lymphoma; Lymphoma, T-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

fludarabine; fludarabine phosphate; Melphalan; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Histiocytosis; Lymphoma, Non-Hodgkin; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Dr. Nelli Bejanyan
• Organization: Moffitt Cancer Center

Nelli.Bejanyan@moffitt.org

813-745-6008

Study Officials

• Nelli Bejanyan, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: December 9, 2019
• Study Start: December 6, 2019
• Primary Completion: February 11, 2024
• Study Completion: February 14, 2024
• Last Updated: December 11, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-12

Locations

US (1)