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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04191187
• Other study ID #: MCC-20131
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 6, 2019
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 37
• Est. completion date: February 2025
• Est. primary completion date: February 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Biphenotypic Acute Leukemia
• Burkitt Lymphoma
• Chronic Myelogenous Leukemia
• Hematologic Neoplasms
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Prolymphocytic
• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoplasmacytic Lymphoma
• Mantle Cell Lymphoma
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Prolymphocytic Leukemia
• Relapsed Chronic Lymphocytic Leukemia
• Relapsed Follicular Lymphoma
• Relapsed Large Cell Lymphoma
• Relapsed Marginal B-cell Lymphoma
• Relapsed Small Lymphocytic Lymphoma
• Relapsed T-Cell Lymphoma
• Undifferentiated Leukemia
• Waldenstrom Macroglobulinemia

Intervention

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

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

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Graft vs Host Disease (GVHD) free survival	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.	At 180 days post-transplant
Secondary	Overall Survival (OS)	OS is defined as the time from the date of PBSCT to the date of death due to any cause.	Up to 18 months
Secondary	Treatment Related Mortality (TRM) at 6 months	TRM is defined as death not directly due to disease	at 6 months post-transplant
Secondary	Treatment Related Mortality (TRM) at 18 months	TRM is defined as death not directly due to disease	at 18 months post-transplant
Secondary	Relapse Free Survival (RFS)	RFS is defined as the time from the date of PBSCT to relapse or death.	Up to 18 months post-transplant

External Links

•   Moffitt Cancer Center Clinical Trials website