IMRT-TMI With Fludarabine as Myeloablative Conditioning for Allogeneic HSCT

NCT03696537 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IUSCC-0652
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes

Keywords

Radiation; Total Marrow Irradiation; Fludarabine; Bone Marrow Transplantation

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) of Total Marrow Irradiation (TMI) in combination with 150 mg/m2 fludarabine- Phase I only

  Day -7 of conditioning regimen through 30 days post transplant (37 days)

• Maximum-tolerated dose (MTD) of Total Marrow Irradiation (TMI) in combination with 150 mg/m2 fludarabine-Phase I only

  Day -7 of conditioning regimen through 30 days post transplant (37 days)

• Overall survival (OS) rate 1 year post transplant-Phase II only

  1 year

Secondary Outcomes (19)

• Frequency of non hematologic toxicities

  100 days

• Incidence of infection

  100 days

• Type of infections

  100 days

• Incidence of graft versus host disease (GvHD)

  100 days

• Incidence of chronic graft versus host disease (GvHD)

  2 years

Study Arms (1)

Fludarabine + Total Marrow Irradiation

EXPERIMENTAL

Drug: Fludarabine; Radiation: Total Marrow Irradiation (TMI)

Interventions

Fludarabine DRUG

Fludarabine 30 mg/m2/day IV (total 5 doses) administered days -7 through -3 of conditioning regimen

Fludarabine + Total Marrow Irradiation

Total Marrow Irradiation (TMI) RADIATION

TMI will be delivered twice a day, at least 6 hours apart, on days -7 through -3 (total of 10 fractions) of conditioning regimen

Fludarabine + Total Marrow Irradiation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be diagnosed with one of the following conditions:
• Acute Myeloid Leukemia (AML) who are not in complete remission, and who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors:
• Duration of first CR \< 6 months (if previously in CR)
• Poor risk karyotype including any of the following: complex karyotype with ≥3 clonal abnormalities, 5q-/-5, 7q-/-7, 11q23 abnormalities, inv(3q), 20q or 21q abnormalities, t(6;9), t(9;22), 17p abnormalities \[or TP53 mutations\] or monosomal karyotype. Molecular typing (except for TP53 mutation) will not be used for eligibility criteria determination.
• Circulating peripheral blood blasts at time of enrollment
• Karnofsky performance status \<90%
• Acute Lymphocytic Leukemia (ALL) who are not in complete remission, and who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors:
• First refractory relapse. Patients in second or subsequent relapse are excluded.
• Donor is CMV seropositive
• Bone marrow blasts \>25% (within 30 days of admission)
• Age \>40 years
• Myelodysplasia with a Revised International Prognostic Score (IPSS-R) of greater than 4.5 (i.e., high- or very-high risk).
• Chronic Myelogenous Leukemia (CML) in either
• Accelerated phase, defined by any of the following:
• % blasts in peripheral blood white cells or bone marrow

You may not qualify if:

• Patients with ALL who are in second or subsequent relapse
• HIV seropositive patients.
• Pregnant or nursing females are excluded from this study.
• Prior radiation therapy
• Patients who have had a prior autologous or allogeneic bone marrow or stem cell transplantation

Sponsors & Collaborators

• Naoyuki G. Saito, M.D., Ph.D.: lead
• Indiana University: collaborator

Study Sites (1)

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Interventions

fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Naoyuki G Saito, MD PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Model Details: Standard "3+3" phase I design of dose escalation using 3 patients per dose level cohort with an expansion to 6 patients at the MTD will be used in Phase I. We will treat 3 patients at the initial dose level of TMI. If no dose-limiting toxicity (DLT) is observed, the next cohort of three patients is treated at the next higher dose level. If 1 of the 3 patients demonstrates DLT, an additional 3 patients are treated at that dose level. If only 1 of the 6 shows DLT, the next cohort of three patients is entered at the next dose level. If 2 or more of the 6 demonstrate DLT, the MTD is defined as the previous dose level. If no DLT is observed in the final dose level, the number of patients treated will be expanded to 6. In phase II, we will enroll additional patients at the defined MTD level. \*Stopping criteria was met during the first dose level cohort in Phase l. The trial will not continue into Phase II as originally planned.

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 4, 2018
• Study Start: August 29, 2018
• Primary Completion: July 8, 2020
• Study Completion: April 13, 2021
• Last Updated: March 9, 2022

Record last verified: 2022-02

Locations

US (1)