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


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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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 CenterMadison, Wisconsin  53792
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical CenterNashville, Tennessee  37232-2516
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Florida Hospital Cancer InstituteOrlando, Florida  32804
Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97201-3098
Massey Cancer Center at Virginia Commonwealth UniversityRichmond, Virginia  23298-0037
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601
Texas Transplant InstituteSan Antonio, Texas  78229
Rocky Mountain Cancer Centers - Denver MidtownDenver, Colorado  80218
Kansas City Cancer Centers - CentralKansas City, Missouri  64111