search
Back to results

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

Primary Purpose

Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
therapeutic allogeneic lymphocytes
cyclosporine
fludarabine phosphate
mycophenolate mofetil
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
radiation therapy
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Rocky Mountain Cancer Centers - Denver Midtown
  • Florida Hospital Cancer Institute
  • Blood and Marrow Transplant Group of Georgia
  • Holden Comprehensive Cancer Center at University of Iowa
  • Kansas City Cancer Centers - Central
  • Cancer Center at Hackensack University Medical Center
  • St. Joseph's Hospital and Medical Center
  • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • Cancer Institute at Oregon Health and Science University
  • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
  • Texas Transplant Institute
  • Massey Cancer Center at Virginia Commonwealth University
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
September 6, 2002
Last Updated
September 13, 2019
Sponsor
University of Texas Southwestern Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT00044954
Brief Title
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

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
November 1999 (Actual)
Primary Completion Date
November 2006 (Actual)
Study Completion Date
November 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert H. Collins, MD
Organizational Affiliation
Simmons Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Rocky Mountain Cancer Centers - Denver Midtown
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Florida Hospital Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Blood and Marrow Transplant Group of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342-4777
Country
United States
Facility Name
Holden Comprehensive Cancer Center at University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1009
Country
United States
Facility Name
Kansas City Cancer Centers - Central
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
James P. Wilmot Cancer Center at University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cancer Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-8590
Country
United States
Facility Name
Texas Transplant Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Massey Cancer Center at Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs