Trials / Recruiting

RecruitingNCT05031897

Two Step Haplo With Radiation Conditioning

A 2 Step Approach to Haploidentical Transplant Using Radiation-Based Reduced Intensity Conditioning

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 63 (estimated)

Sponsor: Thomas Jefferson University · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II clinical trial evaluates whether a modified modality of conditioning reduces treatment-related mortality (TRM) in patients who undergo a hematopoietic stem cell transplant (HSCT) for a hematological malignancy. HSCT is a curative therapy for many hematopoietic malignancies, however this regimen results in higher rates of TRM than other forms of treatment. In recent years, less intense conditioning regimens with radiation and chemotherapy prior to HSCT have been developed. Radiation therapy uses high energy sources to kill cancer cells and shrink tumors while chemotherapy drugs like fludarabine and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study evaluates whether a two-step approach with lower-intensity regimens of these treatments prior to HSCT reduces the rate of TRM.

Detailed description

PRIMARY OBJECTIVE: I. To assess the 2 year cumulative incidence of TRM in patients undergoing reduced intensity conditioning (RIC) haploidentical (HI) HSCT in this protocol. SECONDARY OBJECTIVES: I. To assess the 2 year cumulative incidence of relapse in patients undergoing RIC HI HSCT in this protocol. II. To assess the consistency and pace of engraftment. III. To assess the pace of T cell and B cell immune recovery. IV. To assess the incidence and severity of graft versus host disease (GVHD). OUTLINE: Patients are assigned to 1 of 2 cohorts. RADIATION-BASED COHORT: Patients receive fludarabine intravenously (IV) on days -11, -10, -9, and -8, undergo total-body irradiation (TBI) twice a day (BID) on days -10 and -9, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide IV on days -3 and -2. Patients begin tacrolimus and mycophenolate mofetil IV on day -1. Patients then undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study. CHEMOTHERAPY-BASED COHORT: Patients receive fludarabine IV on days -11, -10, -9, and -8 and melphalan IV on days -10 and -9. Patients undergo TBI and DLI once on day -6. Patients receive cyclophosphamide IV on days -3 and -2 and begin tacrolimus and mycophenolate mofetil on day -1. Patients undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study. After completion of study treatment, patients are followed for 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Fludarabine	Given IV
RADIATION	Total-Body Irradiation	Undergo TBI
PROCEDURE	Donor Lymphocyte Infusion	Undergo DLI
DRUG	Cyclophosphamide	Given IV
DRUG	Tacrolimus	Given IV
DRUG	Mycophenolate Mofetil	Given IV
PROCEDURE	Hematopoietic Cell Transplantation	Undergo HSCT
DRUG	Melphalan	Given IV
PROCEDURE	Bone Marrow Aspiration and Biopsy	Undergo bone marrow aspiration/ biopsy
PROCEDURE	Diagnostic Imaging	Undergo diagnostic imaging
PROCEDURE	Biospecimen Collection	Undergo blood sample collection

Timeline

Start date: 2021-10-25
Primary completion: 2032-04-01
Completion: 2032-04-01
First posted: 2021-09-02
Last updated: 2025-10-30

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05031897. Inclusion in this directory is not an endorsement.