Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00044954
• Other study ID #: CDR0000069461
• Secondary ID: UTSMC-0799296AMG
• Status: Completed
• Phase: Phase 2
• Start date: November 1999
• Est. completion date: November 2006

Study information

• Verified date: September 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining total-body irradiation with fludarabine and donor peripheral stem cell transplantation in treating patients who have hematologic cancer.

Description:

OBJECTIVES:

• Determine the response rate and duration of response in patients with low-risk hematologic malignancies treated with low-dose total-body irradiation (TBI) and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a slow immunosuppression taper and donor leukocyte infusions (DLI).

• Determine the response rate and duration of response in patients with high-risk hematologic malignancies treated with low-dose TBI and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a faster immunosuppression taper and DLI.

• Determine the incidence and extent of graft-versus-host disease, regimen-related toxicity, and engraftment in patients treated with these regimens.

• Assess the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups (high-risk vs low-risk hematologic malignancy). The high-risk group includes acute myelogenous leukemia, myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia (CML), second chronic phase CML, and non-Hodgkin's lymphoma. The low-risk group includes Hodgkin's lymphoma, first chronic phase CML, multiple myeloma, and chronic lymphocytic leukemia.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total-body irradiation on day 0 followed by allogeneic stem cell transplantation. Patients also receive oral mycophenolate mofetil on days 0-28.

High-risk patients receive oral cyclosporine twice daily on days -2 to day 60. Patients with persistent disease, T-cell chimerism, and no graft-vs-host disease (GVHD) on day 90 receive up to 3 doses of donor leukocyte infusion (DLI) over the next 4 months.

Low-risk patients receive oral cyclosporine twice daily on days -2 to day 150. Patients with persistent disease, T-cell chimerism, and no GVHD on day 180 receive up to 3 doses of DLI over the next 4 months.

Quality of life is assessed at baseline and at 1, 3, 6, 9, 12, 18, and 24 months.

Patients are followed at 1, 3, 6, 9, and 12 months and then annually for 2 years.

PROJECTED ACCRUAL: A total of 120 patients (60 per group) will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following hematologic malignancies:

• Chronic myelogenous leukemia (CML)

• First or second chronic phase

• Accelerated phase

• Acute myelogenous leukemia (AML)

• At least second remission

• First remission allowed if poor-risk features are present (complex chromosome karyotype, abnormalities of chromosomes, especially 5 or 7, 12p-, +13, +8, t[9:11])

• Myelodysplastic syndromes (MDS)

• Intermediate- or high-risk disease by the prognostic scoring system

• Multiple myeloma (MM)

• Hodgkin's lymphoma

• Second or greater relapse

• First relapse allowed if disease-free interval is less than 1 year

• Ineligible for autologous transplantation

• Non-Hodgkin's lymphoma (NHL)

• Grade III follicular large cell (relapsed after one course of prior chemotherapy)

• Diffuse large cell (relapsed after one course of prior chemotherapy)

• Mantle cell

• Chronic lymphocytic leukemia (CLL)

• Relapsed after at least 1 course of prior therapy

• Must have 6 out of 6 HLA A-, B-, and DR- identical sibling donor

PATIENT CHARACTERISTICS:

Age

• 18 to 75 for patients with MM

• 50 to 75 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL

• 18 to 49 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL who are considered eligible for an allogeneic bone marrow transplantation (BMT) but do not meet institutional criteria for a standard allogeneic BMT

Performance status

• Zubrod 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• LVEF at least 40% by MUGA or echocardiogram

Pulmonary

• DLCO at least 50% of predicted

Other

• HIV negative

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No recent history of drug or alcohol abuse

• No other prior malignancy except basal cell skin cancer

• No uncontrolled bacterial, viral, fungal, or parasitic infections

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior autologous transplantation allowed if disease progression occurred

• No prior or concurrent tandem autologous transplantation followed by non-myeloablative-allograft protocol

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Preleukemia
• Syndrome

Intervention

Biological:
• therapeutic allogeneic lymphocytes

Drug:
• cyclosporine

• fludarabine phosphate

• mycophenolate mofetil

Procedure:
• allogeneic bone marrow transplantation

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Rocky Mountain Cancer Centers - Denver Midtown	Denver	Colorado
United States	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Kansas City Cancer Centers - Central	Kansas City	Missouri
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Texas Transplant Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States,