NCT04191187CompletedPhase 2
Reduced-Intensity Fludarabine, Melphalan, and Total Body Irradiation Conditioning for Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies
H. Lee Moffitt Cancer Center and Research Institute1 site in 1 country34 target enrollmentStarted: December 6, 2019Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Disease Free Survival
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 DRB
- •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 -DRB
- •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
Arms & Interventions
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)
Intervention: Fludarabine (Drug)
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)
Intervention: Melphalan (Drug)
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)
Intervention: Total Body Irradiation (Radiation)
Outcomes
Primary Outcomes
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 Outcomes
- 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)
Investigators
Study Sites (1)
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