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Trials / Terminated

TerminatedNCT03696537

IMRT-TMI With Fludarabine as Myeloablative Conditioning for Allogeneic HSCT

A Dose Escalation Study of Intensity Modulated Total Marrow Irradiation (IMRT-TMI) With Fludarabine as a Myeloablative Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed and Refractory Hematologic Malignancies

Status
Terminated
Phase
Phase 1
Study type
Interventional
Enrollment
6 (actual)
Sponsor
Naoyuki G. Saito, M.D., Ph.D. · Academic / Other
Sex
All
Age
18 Years – 65 Years
Healthy volunteers
Not accepted

Summary

This is a phase I/II clinical trial on the use of total marrow irradiation (TMI) given concurrently with fludarabine, a chemotherapy drug commonly used to treat leukemia, as a myeloablative therapy for patients undergoing Allo-HSCT. TMI is a targeted technique to deliver radiation to the bone marrow while minimizing dose to other normal organs in the body. In phase I of the clinical study, the dose of radiation to the bone marrow will be incrementally increased to determine the highest tolerated TMI dose. In phase II, the effectiveness of the TMI-fludarabine conditioning regimen utilizing that dose of radiation will be studied. Acute and long-term toxicity data as well as quality of life data will also be studied. \*Stopping criteria was met during the first dose level cohort in Phase l. The trial will not continue into Phase II as originally planned.

Detailed description

This is a phase I/II clinical trial to determine the maximum tolerated dose (MTD) of intensity modulated radiation therapy based total marrow irradiation (TMI) concurrent with fludarabine as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (Allo-HSCT), as well as to determine the efficacy of the regimen in patients with high-risk and relapsed or refractory leukemia and myelodysplasia. TMI, which allows for conformal dosing of target bone marrow tissue while giving lower doses to organs at risk, is considered by many to be a superior alternative to conventional total body irradiation (TBI) Primary Objectives: Phase I: Determine the MTD of TMI given concurrently with fludarabine (fixed at 150 mg/m2) as a conditioning regimen for Allo-HSCT for patients with high risk (relapsed/refractory) acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelogenous leukemia (CML). Phase II: Single-arm exploratory study to expand the cohort at the MTD level to estimate 1- year overall survival (OS), with the objective of increasing the OS from the historical rate of 30% (null hypothesis ) to 50% (alternate hypothesis) with 80% power and a one-sided type I error of 0.05. Secondary Objectives 1. Describe the extramedullary toxicity and the incidence of complications, including mucositis, acute and chronic graft versus host disease (GvHD), sinusoidal obstruction syndrome (SOS), and pneumonitis. 2. Describe the time to engraftment of neutrophils and platelets 3. Describe the disease response rate at day 30 after transplantation 4. Describe the overall survival and disease-free survival 5. Describe the cumulative incidence of relapse and non-relapse mortality 6. Determine the correlation between plasma/serum markers and radiation induced acute and long term toxicities. 7. Describe the quality of life metrics of participating subjects * Stopping criteria was met during the first dose level cohort in Phase l. The trial will not continue into Phase II as originally planned.

Conditions

Interventions

TypeNameDescription
DRUGFludarabineFludarabine 30 mg/m2/day IV (total 5 doses) administered days -7 through -3 of conditioning regimen
RADIATIONTotal Marrow Irradiation (TMI)TMI will be delivered twice a day, at least 6 hours apart, on days -7 through -3 (total of 10 fractions) of conditioning regimen

Timeline

Start date
2018-08-29
Primary completion
2020-07-08
Completion
2021-04-13
First posted
2018-10-04
Last updated
2022-03-09

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03696537. Inclusion in this directory is not an endorsement.