Clinical trial NCT00044954: Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
Official title: Low Dose Total-Body Irradiation And Fludarabine Followed By HLA Matched Allogeneic Stem Cell Transplantation For Hematologic Malgnancies - A Multi-Center Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: 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)
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Midtown
state: Colorado
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - Central
state: Missouri
city: Hackensack
country: United States
facility: Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Richmond
country: United States
facility: Massey Cancer Center at Virginia Commonwealth University
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Simmons Cancer Center
name: Robert H. Collins, MD
role: STUDY_CHAIR
References: