Clinical trial NCT04191187: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
First posted: 2019-12-09
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 \</=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

Primary outcomes:
measure: Disease Free Survival
timeFrame: Up to 18 months post-transplant
Secondary outcomes:
measure: Percentage of Participants With Graft vs Host Disease (GVHD) Free Survival
timeFrame: At 180 days post-transplant
measure: Percentage of Participants Overall Survival (OS)
timeFrame: Up to 18 months
measure: Percentage of Participants With Treatment Related Mortality (TRM) at 6 Months
timeFrame: at 6 months post-transplant
measure: Percentage of Participants With Treatment Related Mortality (TRM) at 18 Months
timeFrame: at 18 months post-transplant
measure: Percentage of Participants With Relapse Free Survival (RFS)
timeFrame: Up to 18 months post-transplant
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: Moffitt Cancer Center
name: Nelli Bejanyan, MD
role: PRINCIPAL_INVESTIGATOR
References: