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

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00044954

Collaborator

(none)

Locations

Actual Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 1999

Actual Primary Completion Date :

Nov 1, 2006

Actual Study Completion Date :

Nov 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Centers - Denver Midtown	Denver	Colorado	United States	80218
2	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
3	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342-4777
4	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
5	Kansas City Cancer Centers - Central	Kansas City	Missouri	United States	64111
6	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
8	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
9	Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
10	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee	United States	37212
11	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75235-8590
12	Texas Transplant Institute	San Antonio	Texas	United States	78229
13	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0037
14	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792