Total Marrow and Total Lymph Node Irradiation, Fludarabine, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Hematological Cancer That Has Not Responded to Treatment

NCT ID: NCT00800150

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2010-10-31

Brief Summary

RATIONALE: Giving total marrow and total lymph node irradiation together with low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase I trial is studying the side effects and best dose of total marrow and total lymph node irradiation when given together with fludarabine and melphalan followed by donor stem cell transplant in treating patients with advanced hematological cancer that has not responded to treatment.

Detailed Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation (TMLI) using helical tomotherapy in combination with a reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in patients undergoing allogeneic hematopoietic stem cell transplantation for advanced, relapsed or refractory hematological malignancies.
• To describe the toxicities of escalating doses of TMLI in these patients.

Secondary

• To describe the frequency of clinical response in patients treated with this regimen.
• To describe the frequency of primary and secondary engraftment failure in patients treated with this regimen.
• To describe the time to neutrophil and platelet engraftment in patients treated with this regimen.
• To describe the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
• To describe the overall survival of patients treated with this regimen.
• To describe the progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node irradiation (TMLI).

• Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow, major lymph node chains, spleen, and liver using helical tomotherapy twice daily on days -6 to -3.
• Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and melphalan IV on day -1.
• Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.

After completion of study treatment, patients are followed periodically.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Study Design

• Primary Study Purpose: TREATMENT

Interventions

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

intensity-modulated radiation therapy

Intervention Type: RADIATION

tomotherapy

Intervention Type: RADIATION

total marrow irradiation

Intervention Type: RADIATION

total nodal irradiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Patients 16-50 years of age must meet ≥ 1 of the following criteria:

• Ejection fraction 50-60% by MUGA scan and/or echocardiogram
• DLCO 50-75% of predicted
• Creatinine clearance or GFR 60-80 mL/min
• Serum bilirubin ≤ 2.0 mg/dL
• SGOT and SGPT 1.5-5 times upper limit of normal
• No other medical and/or psychosocial problem that, in the opinion of the primary physician or principal investigator, would place the patient at unacceptable risk from study regimen
• No Fanconi anemia
• HLA-identical sibling OR matched unrelated donor available

PATIENT CHARACTERISTICS:

• Zubrod or Karnofsky performance status 70-100%
• Negative pregnancy test
• Able to lie supine in a full body cast for 30 minutes
• No HIV infection
• No evidence of active hepatitis B or C infection
• No evidence of cirrhosis
• No uncontrolled viral, bacterial, or fungal infection within the past 4 weeks
• No radiographic changes indicating pulmonary disease (e.g., pulmonary nodules, infiltrates, or pleural effusion) unless cleared by pulmonary biopsy that shows no evidence of active pulmonary disease
• No major medical or psychiatric disorder that would seriously compromise patient tolerance of study regimen

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior radiation therapy

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Rosenthal, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-08076

Identifier Type: -

Identifier Source: secondary_id

CDR0000626148

Identifier Type: REGISTRY

Identifier Source: secondary_id

08076

Identifier Type: -

Identifier Source: org_study_id