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

• ClinicalTrials.gov Identifier: NCT04191187
• Recruitment Status: Active, not recruiting
• First Posted: December 9, 2019
• Last Update Posted: January 11, 2023
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia; Acute Lymphoblastic 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 Chronic Lymphocytic Leukemia; Relapsed Small Lymphocytic Lymphoma; Relapsed Marginal B-cell Lymphoma; Relapsed Follicular Lymphoma; Lymphoplasmacytic Lymphoma	Drug: Fludarabine; Drug: Melphalan; Radiation: Total Body Irradiation	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 6, 2019
• Estimated Primary Completion Date: February 11, 2024
• Estimated Study Completion Date: February 2025

Arms and Interventions

Arm

Intervention/treatment

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)

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; Other Name: Fludara; 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.; Other Name: Alkeran; Radiation: Total Body Irradiation; Total Body Irradiation (TBI) will be delivered at a dose of 200 centigray units (cGy)

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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.
2. 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.
3. Treatment Related Mortality (TRM) at 6 months [ Time Frame: at 6 months post-transplant ]
   TRM is defined as death not directly due to disease
4. Treatment Related Mortality (TRM) at 18 months [ Time Frame: at 18 months post-transplant ]
   TRM is defined as death not directly due to disease
5. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 </=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:
• Progressed within 12 months of achieving a partial or complete remission Patients who had remissions lasting up
• Patients who had remission lasting > 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

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Hany Elmariah, MD, MS; Moffitt Cancer Center
• Principal Investigator: Nelli Bejanyan, MD; Moffitt Cancer Center

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT04191187
• Other Study ID Numbers: MCC-20131
• First Posted: December 9, 2019
• Last Update Posted: January 11, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Burkitt Lymphoma; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Lymphoma, Mantle-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Leukemia, Prolymphocytic; Waldenstrom Macroglobulinemia; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases