Targeted Marrow Irradiation, Fludarabine Phosphate, and Busulfan Before Donor Progenitor Cell Transplant in Treating Patients With Hematologic Malignancies

NCT02129582 | Completed Phase 1 FDA Drug

• 1 other identifier: CASE9Z13
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of targeted marrow irradiation when given with fludarabine phosphate and busulfan before donor progenitor cell transplant in treating patients with hematologic malignancies. Targeted marrow irradiation is a type of specialized radiation therapy that delivers a high dose of radiation directly to the cancer cells, which may kill more cancer cells and cause less damage to normal cells. Giving targeted marrow irradiation and chemotherapy drugs, such as fludarabine phosphate and busulfan, before a donor progenitor cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's progenitor cells. When the healthy progenitor cells from a donor are infused into the patient they may help the patient's bone marrow make progenitor cells, red blood cells, white blood cells, and platelets.

Conditions

Acute Myeloid Leukemia; Hematologic Malignancies; Acute Lymphocytic Leukemia; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Myelofibrosis; Myeloproliferative Syndrome

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of targeted marrow irradiation defined as the dose level immediately below that in which greater than or equal to 2/6 subjects experience a dose limiting toxicity assessed using NCI CTCAE version 4.0

  Up to day 32

Secondary Outcomes (8)

• Incidence of toxicities assessed using NCI CTCAE version 4.0

  Up to day 32

• Patient mortality

  Day 100

• Organ avoidance

  Up to 12 months

• Target coverage

  Up to 12 months

• Planning time

  Up to 12 months

Study Arms (1)

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

EXPERIMENTAL

CONDITIONING: Patients undergo TMI BID on days -10 to -7. Patients also receive fludarabine phosphate IV over 1 hour on days -6 to -2 and busulfan IV or PO on days -5 and -4. TRANSPLANT: Patients undergo allogeneic hematopoietic progenitor cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 and -2, tacrolimus IV or PO beginning on day -1 for at least 6 months with taper beginning at 4 months, and methotrexate IV on days 1, 3, 6, and 11.

Radiation: total marrow irradiation; Drug: fludarabine phosphate; Drug: busulfan; Procedure: myeloid progenitor cell transplantation; Biological: anti-thymocyte globulin; Drug: tacrolimus; Drug: methotrexate; Other: laboratory biomarker analysis

Interventions

total marrow irradiation RADIATION

Undergo TMI

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

busulfan DRUG

Given IV or PO

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

myeloid progenitor cell transplantation PROCEDURE

Undergo allogeneic hematopoietic progenitor cell transplant

Also known as: MPCT

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

anti-thymocyte globulin BIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Prograf

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (TMI, fludarabine, busulfan, allogeneic HPCT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ineligible to receive full myeloablative conditioning regimen for allogeneic hematopoietic progenitor cell transplant due to age or comorbidities
• Patients must have histologically or cytologically diagnosis of hematologic malignancies with an indication for allogeneic hematopoietic progenitor cell transplantation, who are ineligible to receive a full ablative conditioning regimen as part of their transplantation, including:
• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Non Hodgkin lymphoma
• Hodgkin lymphoma
• Multiple myeloma
• Myelodysplastic syndrome
• Chronic lymphocytic leukemia
• Chronic myeloid leukemia:
• Myeloproliferative syndromes including myelofibrosis
• Complete remission is not necessary for enrollment in this protocol
• Patients must have an allogeneic hematopoietic progenitor cell donor (HPCT), either a matched sibling, mismatched (1 allele) sibling, or a matched unrelated donor (MUD) or a mismatched (1 allele) unrelated donor
• Previous hematopoietic progenitor cell transplantation is allowed; a minimum of 6 months should have elapsed from prior autologous hematopoietic progenitor cell transplantation and a minimum of 6 months should have elapsed since prior allogeneic hematopoietic progenitor cell transplantation; prior transplantation with conditioning regimens using total body irradiation is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

You may not qualify if:

• Prior non-hematologic treatment toxicities must be resolved to ≤ grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, with the exception of the following grade 2 toxicities: alopecia; dry skin; spleen disorders, hearing impairment; tinnitus; hypothyroidism; hyperthyroidism; endocrine disorders; blurred vision; cataracts; constipation; gastroesophageal reflux; fatigue; abnormal coagulation tests INR and/or aPTT; weight gain or weight loss; anorexia; glucose intolerance; hypoalbuminemia; hypokalemia; muscle weakness; dysgeusia; paresthesias; peripheral motor and/or sensory neuropathy; hot flashes; hypertension.
• Patients must not have received other investigational agents within 14 days of initiation of the conditioning regimen
• Patients with untreated brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine and or busulfan or other agents used in this study
• Prior allogeneic hematopoietic progenitor cell transplantation
• Prior autologous hematopoietic progenitor cell transplantation if the conditioning regimen included total body irradiation
• Pregnant or breastfeeding women are excluded from this study; breastfeeding should be discontinued
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients with a history of therapy with radiation therapy are excluded
• Due to technical limitations of TMI, patients must be no taller than 1.9 m (6 feet 4 inches), and no wider from elbow to elbow in the supine position than 60 cm.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndromes; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Primary Myelofibrosis

Interventions

fludarabine phosphate; Busulfan; Antilymphocyte Serum; thymoglobulin; Tacrolimus; Methotrexate; merphos

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Site; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Molly Gallogly, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: November 5, 2014
• Primary Completion: March 15, 2019
• Study Completion: March 5, 2020
• Last Updated: May 7, 2021

Record last verified: 2021-05

Locations

US (1)