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Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
therapeutic allogeneic lymphocytes
cyclosporine
cytarabine
fludarabine phosphate
methotrexate
mycophenolate mofetil
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
radiation therapy
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of acute lymphoblastic leukemia (ALL) Adult patients must meet 1 of the following criteria: Age 50 to 75 with high-risk ALL in complete remission (CR) (less than 5% blasts by morphology on bone marrow aspirate and absence of peripheral blasts) or ALL in second CR (CR2) or greater Age 18 to 50 with high-risk ALL in first CR (CR1) and either ineligible for conventional allogeneic transplantation (based on general medical condition) or refused conventional transplantation High-risk adult ALL in CR1 includes patients meeting 1 or more of the following criteria: Age 30 and over Non-T-cell phenotype Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7 Failure to achieve CR after 4 weeks of induction chemotherapy Age 18 to 50 with ALL in CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition Age 18 to 50 with high-risk ALL in CR2 or greater and refused conventional allogeneic transplantation Pediatric patients must meet 1 of the following criteria: Under age 18 with high-risk ALL in CR1 and ineligible for conventional allogeneic transplantation based on general medical condition High-risk pediatric ALL in CR1 includes patients meeting 1 or more of the following criteria: Cytogenetic abnormalities t(9;22) with WBC at least 25,000/mm3 at diagnosis t(4;11) in patients under age 1 or age 10 and over Hypodiploidy (no more than 45 chromosomes) Failure to achieve CR after 4 weeks of induction chemotherapy Persistent peripheral blasts after 1 week of induction chemotherapy Under age 18 with CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition Age 12 and under allowed if approved by the principle investigator No active CNS disease Availability of a sibling donor (excluding an identical twin) HLA genotypically identical for at least 1 haplotype HLA-A, -B, -C, -DRB1, and -DQB1 genotypically or phenotypically identical PATIENT CHARACTERISTICS: Age: See Disease Characteristics 75 and under Performance status: Karnofsky 50-100% (adults) Lansky 40-100% (children) Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: No fulminant liver failure No alcoholic hepatitis No history of bleeding esophageal varices No grade II or greater hepatic encephalopathy No hepatic synthetic dysfunction evidenced by prolongation of PT with INR greater than 2.5 No intractable ascites related to portal hypertension No bacterial or fungal liver abscess No chronic viral hepatitis with bilirubin greater than 5 mg/dL No biliary obstruction with bilirubin greater than 5 mg/dL No concurrent symptomatic biliary disease Renal: Not specified Cardiovascular: Cardiac ejection fraction at least 30% Pulmonary: No requirement for supplementary continuous oxygen Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception during and for 1 year after study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent posttransplantation growth factors during mycophenolate mofetil administration Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Sites / Locations

  • Cancer Institute at Oregon Health and Science University
  • Fred Hutchinson Cancer Research Center
  • Universitaet Leipzig

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 7, 2001
Last Updated
November 28, 2011
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00027547
Brief Title
Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia
Official Title
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
Study Type
Interventional

2. Study Status

Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and donor white blood cells may prevent this from happening. PURPOSE: Phase I/II trial to determine the effectiveness of combination chemotherapy and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia.
Detailed Description
OBJECTIVES: Determine if a one-year disease free survival of 40% and a day 200 transplant-related mortality of less than 25% can be achieved in patients with high-risk acute lymphoblastic leukemia in complete remission treated with a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation followed by allogeneic peripheral blood stem cell or bone marrow transplantation. Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of minimal residual disease after nonmyeloablative allografting in these patients. OUTLINE: This is a multicenter study. Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days -4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0. Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0. Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27. Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a total of 3 doses (if necessary). Patients without a history of CNS leukemia and patients with a history of CNS leukemia previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS leukemia not previously treated with craniospinal irradiation undergo craniospinal irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of 6 doses beginning on day 32 after transplantation. Male patients also undergo testicular radiotherapy for 7 days. Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months. PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, 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)
cytarabine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
methotrexate
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
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of acute lymphoblastic leukemia (ALL) Adult patients must meet 1 of the following criteria: Age 50 to 75 with high-risk ALL in complete remission (CR) (less than 5% blasts by morphology on bone marrow aspirate and absence of peripheral blasts) or ALL in second CR (CR2) or greater Age 18 to 50 with high-risk ALL in first CR (CR1) and either ineligible for conventional allogeneic transplantation (based on general medical condition) or refused conventional transplantation High-risk adult ALL in CR1 includes patients meeting 1 or more of the following criteria: Age 30 and over Non-T-cell phenotype Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7 Failure to achieve CR after 4 weeks of induction chemotherapy Age 18 to 50 with ALL in CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition Age 18 to 50 with high-risk ALL in CR2 or greater and refused conventional allogeneic transplantation Pediatric patients must meet 1 of the following criteria: Under age 18 with high-risk ALL in CR1 and ineligible for conventional allogeneic transplantation based on general medical condition High-risk pediatric ALL in CR1 includes patients meeting 1 or more of the following criteria: Cytogenetic abnormalities t(9;22) with WBC at least 25,000/mm3 at diagnosis t(4;11) in patients under age 1 or age 10 and over Hypodiploidy (no more than 45 chromosomes) Failure to achieve CR after 4 weeks of induction chemotherapy Persistent peripheral blasts after 1 week of induction chemotherapy Under age 18 with CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition Age 12 and under allowed if approved by the principle investigator No active CNS disease Availability of a sibling donor (excluding an identical twin) HLA genotypically identical for at least 1 haplotype HLA-A, -B, -C, -DRB1, and -DQB1 genotypically or phenotypically identical PATIENT CHARACTERISTICS: Age: See Disease Characteristics 75 and under Performance status: Karnofsky 50-100% (adults) Lansky 40-100% (children) Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: No fulminant liver failure No alcoholic hepatitis No history of bleeding esophageal varices No grade II or greater hepatic encephalopathy No hepatic synthetic dysfunction evidenced by prolongation of PT with INR greater than 2.5 No intractable ascites related to portal hypertension No bacterial or fungal liver abscess No chronic viral hepatitis with bilirubin greater than 5 mg/dL No biliary obstruction with bilirubin greater than 5 mg/dL No concurrent symptomatic biliary disease Renal: Not specified Cardiovascular: Cardiac ejection fraction at least 30% Pulmonary: No requirement for supplementary continuous oxygen Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception during and for 1 year after study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent posttransplantation growth factors during mycophenolate mofetil administration Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Georges, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Cancer Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
Universitaet Leipzig
City
Leipzig
ZIP/Postal Code
D-04103
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia

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