- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00031655
Reduced Intensity Donor Stem Cell Transplant in Treating Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Unrelated Donors for Treatment of Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission - A Multicenter Trial
Study Overview
Status
Conditions
Intervention / Treatment
- Other: laboratory biomarker analysis
- Drug: fludarabine phosphate
- Radiation: total-body irradiation
- Drug: mycophenolate mofetil
- Drug: cyclosporine
- Biological: donor lymphocytes
- Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
- Procedure: peripheral blood stem cell transplantation
Detailed Description
PRIMARY OBJECTIVES:
I. To determine if a one-year disease-free survival (DFS) of > 25% can be achieved among adult patients with high risk acute lymphocytic leukemia (ALL) in complete remission (CR) who undergo nonmyeloablative allografting.
II. To determine if a one-year DFS of >= 40% can be achieved among pediatric patients with high risk ALL in CR who undergo nonmyeloablative allografting.
SECONDARY OBJECTIVES:
I. To determine if a day +200 transplant-related mortality (TRM) of < 25% can be achieved among patients with high risk ALL in CR who undergo nonmyeloablative allografting.
II. To evaluate the efficacy and toxicity of donor lymphocyte infusion (DLI) in the treatment of minimal residue disease (MRD) after nonmyeloablative allografting for patients with high risk ALL in CR.
OUTLINE:
NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo total body irradiation (TBI) on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients with minimal residual disease may receive donor lymphocyte infusion IV.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO very 8 hours on days 0 to 40 with taper to day 96.
After completion of study treatment, patients are followed up at days 28, 56, 84, 120, 180, and 360; at 18 months; and annually for up to 5 years.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States
- Oregon Health and Sciences University
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Seattle, Washington, United States, 98108
- Veterans Affairs Puget Sound Healthcare System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ADULT PATIENTS:
- Patients 50-75 years old with high risk ALL in first CR (CR1) or ALL in CR >= second CR (CR2)
- Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who are not eligible for a conventional allogeneic transplantation based on general medical condition
- Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who refuse a conventional allogeneic transplant
- Patients >= 18 years old and < 50 years old with ALL in CR >= CR2 who are not eligible for a conventional allogeneic transplantation based on general medical condition
- Patients >= 18 years old and < 50 years old with high risk ALL in CR >= CR2 who refuse a conventional allogeneic transplant
- CR is defined as < 5% blasts by morphology on a bone marrow aspirate and the absence of peripheral blasts
High risk adult ALL in CR1 includes those patients with one or more of the following:
- Age >=30 years
- 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
- PEDIATRIC PATIENTS:
- Patients < 18 years old with ALL in high risk CR1 who are not candidates for conventional allogeneic transplantation based on general medical condition
- Patients < 18 years old with ALL in CR >= CR2 who are not candidates for conventional allogeneic transplantation based on general medical condition
- Patients < 12 years old require approval by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator prior to enrollment
- CR is defined as < 5% blasts by morphology on a bone marrow aspirate and absence of peripheral blasts
High risk pediatric ALL in CR1 includes those patients with one or more of the following:
Cytogenetic abnormalities including:
- t(9;22) with a white blood cell (WBC) >= 25,000 at diagnosis or
- t(4;11) in patients < 1 year old and >= 10 years old or
- Hypodiploidy (< 45 chromosomes)
- Failure to achieve CR after 4 weeks of induction chemotherapy
- Persistent peripheral blasts after one week of induction chemotherapy
DONOR: FHCRC matching Grade 2.1: Unrelated donors who are prospectively:
- Matched for human leukocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing) and
- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
- DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT); if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results
- DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
- DONOR: Donor must consent to peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor centers
Exclusion Criteria:
- Active central nervous system (CNS) disease
- Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Pregnancy or breastfeeding
- Human immunodeficiency virus (HIV) seropositivity
- ORGAN DYSFUNCTION, ADULT CRITERIA:
- Requiring supplementary continuous oxygen OR diffusing capacity of the lung for carbon monoxide (DLCO) < 40%
- Cardiac ejection fraction < 35%
- Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
- Karnofsky performance score < 50
- ORGAN DYSFUNCTION, PEDIATRIC CRITERIA:
- Lansky play-performance score < 40
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (nonmyeloablative allogeneic PBSCT)
NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Patients with minimal residual disease may receive donor lymphocyte infusion IV. IMMUNOSUPPRESSION: Patients receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO very 8 hours on days 0 to 40 with taper to day 96. |
Correlative studies
Given IV
Other Names:
Undergo TBI
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given IV
Undergo nonmyeloablative allogeneic PBSCT
Undergo nonmyeloablative allogeneic PBSCT
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Leukemia-free survival
Time Frame: 1 year
|
Incidence of survival without relapse.
Kaplan-Meier estimates will be used to estimate one-year leukemia-free survival.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 1 year
|
1 year
|
Incidence of relapse
Time Frame: 1 year
|
1 year
|
Transplant-related mortality
Time Frame: Day +200
|
Day +200
|
Transplant-related mortality
Time Frame: 1 year
|
1 year
|
Efficacy of DLI for the elimination of MRD
Time Frame: Up to day 120
|
Up to day 120
|
Toxicity of DLT, graded using a modified version of the National Cancer Institute (NCI) Common Toxicity Criteria
Time Frame: Up to 5 years
|
Up to 5 years
|
Incidence of rejection
Time Frame: 1 year
|
1 year
|
Incidence of acute grade II-IV graft-versus-host disease (GVHD) and chronic GVHD, graded using a modified version of the National Cancer Institute (NCI) Common Toxicity Criteria
Time Frame: Up to 5 years
|
Up to 5 years
|
Karnofsky performance score and Lansky performance score
Time Frame: 1 year
|
1 year
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: George Georges, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia
- Recurrence
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 1623.00
- P01CA018029 (U.S. NIH Grant/Contract)
- NCI-2012-00580 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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