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

Sponsor

H. Lee Moffitt Cancer Center and Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04191187

Collaborator

(none)

Enrollment

Location

Arm

83.8

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Dec 6, 2019

Anticipated Primary Completion Date :

Nov 11, 2024

Anticipated Study Completion Date :

Dec 1, 2026

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

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 Names:

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 Names:

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

Disease Free Survival [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

Graft vs Host Disease (GVHD) free survival [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) [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 [at 6 months post-transplant]
TRM is defined as death not directly due to disease
Treatment Related Mortality (TRM) at 18 months [at 18 months post-transplant]
TRM is defined as death not directly due to disease
Relapse Free Survival (RFS) [Up to 18 months post-transplant]
RFS is defined as the time from the date of PBSCT to relapse or death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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