Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study
18 Years
75 Years
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Trial Information
Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Robert H. Collins, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Simmons Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000069461
NCT ID:
NCT00044954
Start Date:
November 2001
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Diseases
- recurrent adult Hodgkin lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- adult acute myeloid leukemia in remission
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse large cell lymphoma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- recurrent mantle cell lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- refractory multiple myeloma
- stage I mantle cell lymphoma
- contiguous stage II mantle cell lymphoma
- noncontiguous stage II mantle cell lymphoma
- atypical chronic myeloid leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- refractory chronic lymphocytic leukemia
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center | Nashville, Tennessee 37232-2516 |
| St. Joseph's Hospital and Medical Center | Paterson, New Jersey 07503 |
| Florida Hospital Cancer Institute | Orlando, Florida 32804 |
| Cancer Institute at Oregon Health and Science University | Portland, Oregon 97201-3098 |
| Massey Cancer Center at Virginia Commonwealth University | Richmond, Virginia 23298-0037 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| Cancer Center at Hackensack University Medical Center | Hackensack, New Jersey 07601 |
| Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390-9063 |
| Blood and Marrow Transplant Group of Georgia | Atlanta, Georgia 30342-1601 |
| Texas Transplant Institute | San Antonio, Texas 78229 |
| Rocky Mountain Cancer Centers - Denver Midtown | Denver, Colorado 80218 |
| Kansas City Cancer Centers - Central | Kansas City, Missouri 64111 |
