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| Sponsor: | Fred Hutchinson Cancer Research Center |
|---|---|
| Collaborator: |
National Cancer Institute (NCI) |
| Information provided by: | Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00036738 |
Purpose
This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Acute Lymphoblastic Leukemia in Remission Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Relapsing Chronic Myelogenous Leukemia |
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Drug: imatinib mesylate Drug: dasatinib Drug: nilotinib Radiation: total-body irradiation Drug: cyclosporine Drug: mycophenolate mofetil Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation Biological: therapeutic allogeneic lymphocytes Genetic: polymerase chain reaction Other: flow cytometry Genetic: fluorescence in situ hybridization Other: laboratory biomarker analysis |
Phase II |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Allogeneic Nonmyeloablative Hematopoietic Stem Cell Transplant for Patients With BCR-ABL Tyrosine Kinase Inhibitor Responsive Ph+ Acute Leukemia - a Multi-Center Trial |
| Estimated Enrollment: | 30 |
| Study Start Date: | July 2001 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (allogeneic nonmyeloablative HSCT)
See Detailed Description
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Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic HSCT
Drug: imatinib mesylate
Given PO
Other Names:
Drug: dasatinib
Given PO
Other Names:
Drug: nilotinib
Given PO
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: cyclosporine
Given IV or PO
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Drug: fludarabine phosphate
Given IV
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo PBSC transplant
Other Names:
Biological: therapeutic allogeneic lymphocytes
Given IV
Other Name: ALLOLYMPH
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: flow cytometry
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Other: laboratory biomarker analysis
Correlative studies
|
PRIMARY OBJECTIVES:
I. To determine whether the rate of leukemia relapse can be decreased for patients with chronic myelogenous leukemia in blast crisis (CML-BC) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) responsive to imatinib mesylate (or either dasatinib or nilotinib for patients who have imatinib-resistant disease or who are intolerant of imatinib) followed by nonmyeloablative hematopoietic stem cell transplantation (HSCT) compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy.
II. To determine whether the rate of transplantation-related mortality (TRM) can be decreased for patients with CML-BC and Ph+ ALL responsive to imatinib mesylate (or dasatinib or nilotinib) followed by nonmyeloablative HSCT compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with mixed or full donor chimerism as preemptive therapy to eliminate minimal residual disease.
OUTLINE:
INDUCTION THERAPY: Patients continue to receive imatinib mesylate orally (PO), dasatinib PO, or nilotinib PO once or twice daily until day -2 and resume on day 14 or when blood counts recover after peripheral blood stem cell (PBSC) transplantation.
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine intravenously (IV) on days -4 to -2; and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic PBSC transplantation on day 0.
GRAFT-VERSUS-HOST-DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil (MMF) PO every 12 hours on days 0-27 (related donor recipients) or every 8 hours on days 0-96 with taper on day 40 (unrelated donor recipients). Patients also receive cyclosporine IV or PO every 8 or 12 hours on days -3 to 56, followed by taper on days 57-180 (related donor recipients) or on days -3 to 100, followed by taper on days 101-177 (unrelated donor recipients).
DONOR LYMPHOCYTE INFUSION: Patients with persistent disease and no GVHD after stopping GVHD prophylaxis receive donor lymphocyte infusion IV over 30 minutes once every 28 days for 3 doses.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed up periodically for 2 years and then annually thereafter for 5 years.
Eligibility| Ages Eligible for Study: | up to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
RELATED DONOR:
HLA-MATCHED UNRELATED DONOR:
Exclusion Criteria:
RELATED DONORS:
HLA-MATCHED UNRELATED DONORS:
Contacts and Locations| United States, Colorado | |
| Presbyterian - Saint Lukes Medical Center - Health One | Recruiting |
| Denver, Colorado, United States, 80218 | |
| Contact: Michael B. Maris 303-777-2663 | |
| Principal Investigator: Michael B. Maris | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: George E. Georges 206-667-6886 | |
| Principal Investigator: George E. Georges | |
| VA Puget Sound Health Care System | Recruiting |
| Seattle, Washington, United States, 98101 | |
| Contact: William H. Schubach 206-762-1010 | |
| Principal Investigator: William H. Schubach | |
| Principal Investigator: | George Georges | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
| Responsible Party: | Georges, George, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00036738 History of Changes |
| Other Study ID Numbers: | 1581.00, NCI-2010-00131, P01CA018029, P01CA078902 |
| Study First Received: | May 13, 2002 |
| Last Updated: | January 9, 2012 |
| Health Authority: | United States: Federal Government |
|
Blast Crisis Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Philadelphia Chromosome Neoplasms by Histologic Type Neoplasms Cell Transformation, Neoplastic Neoplastic Processes Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Pathologic Processes Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Translocation, Genetic Chromosome Aberrations Cyclosporine Cyclosporins Mycophenolic Acid Imatinib Dasatinib Fludarabine monophosphate Mycophenolate mofetil Vidarabine |