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

Information source: Case Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: 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

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

Phase: Phase 1

Status: Recruiting

Sponsored by: Case Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Paolo Caimi, Principal Investigator, Affiliation: Case Comprehensive Cancer Center

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.

Clinical Details

Official title: Phase I Trial of Escalated Doses of Targeted Marrow Irradiation (TMI) Combined With Fludarabine and Busulfan as Conditioning Regimen for Allogeneic Hematopoietic Progenitor Cell Transplantation

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

Incidence of toxicities assessed using NCI CTCAE version 4.0

Patient mortality

Organ avoidance

Target coverage

Planning time

Treatment delivery time

Disease response status, assessed by standard criteria for the presence of relapse

Rates of acute GVHD, graded and staged according to the Blood and Marrow Transplant Clinical Trials Network Manual of Operations

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of targeted marrow irradiation given in combination with fludarabine (fludarabine phosphate) and busulfan as conditioning regimen for allogeneic hematopoietic progenitor cell transplantation. SECONDARY OBJECTIVES: I. To describe the toxicity profile of the conditioning regimen of targeted marrow irradiation (TMI), fludarabine and busulfan for allogeneic hematopoietic progenitor transplantation. II. To describe the use of two techniques of delivering TMI, volumetric modulated arc therapy (VMAT) and TomoTherapy, on patient's computed tomography (CT) simulation images and describe differences in organ avoidance and target coverage, planning time, and treatment delivery time. III. To determine the disease response status 100 days after allogeneic hematopoietic progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and busulfan. IV. To determine the rates of acute graft versus host disease after allogeneic hematopoietic progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and busulfan. OUTLINE: This is a dose-escalation study of TMI.

CONDITIONING: Patients undergo TMI twice daily (BID) on days - 10 to -7. Patients also

receive fludarabine phosphate intravenously (IV) over 1 hour on days - 6 to -2 and busulfan

IV or orally (PO) on days - 5 and -4.

TRANSPLANT: Patients undergo allogeneic hematopoietic progenitor cell transplant on day 0. GRAFT-VERSUS-HOST DISEASE (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. After completion of study treatment, patients are followed up at 100 days, 6 months, and 12 months.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have histologically or cytologically diagnosis of hematologic

malignancies, including:

- Acute myeloid leukemia

- Acute lymphocytic leukemia

- Non Hodgkin lymphoma

- Hodgkin lymphoma

- Multiple myeloma

- Myelodysplastic syndrome

- Chronic lymphocytic leukemia

- Chronic myeloid leukemia:

- In chronic phase that has failed therapy with at least 3 different tyrosine

kinase inhibitors or has progressed to accelerated or blast phase

- In accelerated or blast crisis

- Myeloproliferative syndromes including myelofibrosis

- Complete remission is not necessary for enrollment in this protocol, however

Hodgkin and non Hodgkin lymphoma must have had remission of all extramedullary disease to be eligible to participate in this trial

- Require an allogeneic hematopoietic progenitor cell transplantation (HPCT) from

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

- Life expectancy of > 12 weeks, in the opinion of and as documented by the

investigator

- Patients must have adequate hepatic, and renal function as defined; there is no

exclusion for the presence of cytopenias

- Total bilirubin =< 1. 5 times the institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<

2. 5 X institutional upper limit of normal

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2. 5

X institutional upper limit of normal

- Creatinine clearance (calculated by the Cockroft-Gault formula) >= 30 ml/min

- Women of child-bearing potential and men must agree to use adequate contraception

(double barrier method of birth control or abstinence) from the time of study entry, for the duration of study participation and for 3 months after completing treatment; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately

- Subjects must have the ability to understand and the willingness to sign a written

informed consent document Exclusion Criteria:

- 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

- 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

- Patients with uncontrolled intercurrent illness including, but not limited to ongoing

or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; this exclusion criterion does not include the underlying disease for which the patient is undergoing hematopoietic progenitor cell transplantation

- 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

Locations and Contacts

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio 44106-5065, United States; Recruiting
Paolo F. Caimi, Phone: 216-844-0139, Email: paolo.caimi@case.edu
Paolo F. Caimi, Principal Investigator
Additional Information

Starting date: June 2014
Last updated: March 24, 2015

Page last updated: August 23, 2015

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