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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
Temporarily Closed
Cancer Type
Lymphoma
Myelodysplastic Syndromes (MDS)
Trial Phase
Phase I
Phase II
Eligibility
18 - 65 Years, Male and Female
Study Type
Treatment
NCD ID
NCT03696537
Protocol IDs
IUSCC-0652 (primary)
NCI-2018-02544
Study Sponsor
Indiana University / Melvin and Bren Simon Cancer Center

Summary

This phase I / II trial studies the best dose and side effects of total marrow irradiation and how well it works with fludarabine as a conditioning regimen for patients with hematologic malignancies that has come back or does not respond to treatment and are undergoing donor stem cell transplantation. Total marrow irradiation is a type of radiation therapy and a form of total body irradiation that may deliver focused radiation to the major marrow sites where cancer cells reside. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total marrow irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells.

Objectives

PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of total marrow irradiation (TMI) given concurrently with fludarabine (fixed at 150 mg/m^2) as a conditioning regimen for allogeneic (Allo)-hematopoietic stem cell transplantation (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 I)
II. 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. (Phase II)

SECONDARY OBJECTIVES:
I. 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.
II. Describe the time to engraftment of neutrophils and platelets.
III. Describe the disease response rate at day 30 after transplantation.
IV. Describe the overall survival and disease-free survival.
V. Describe the cumulative incidence of relapse and non-relapse mortality.
VI. Determine the correlation between plasma/serum markers and radiation induced acute and long term toxicities.
VII. Describe the quality of life metrics of participating subjects.

OUTLINE: This is a dose-escalation study of total marrow irradiation.

Patients receive fludarabine intravenously (IV) on days -7 to -3 and undergo total marrow irradiation twice daily on days -7 to -3. Patients then undergo allogeneic hematopoietic stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 30, 100, 180 and 365 days, and then annually for up to 3 years.
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