Biological Therapy in Treating Patients With Advanced Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia Who Are Undergoing
Stem Cell Transplantation
This study is not yet open for patient recruitment.
Sponsored by: |
Fred Hutchinson Cancer Research Center
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Information provided by: |
National Cancer Institute (NCI) |
Purpose
RATIONALE: Biological therapies work in different ways to stimulate the immune system and stop cancer cells from growing.
Combining different types of biological therapies may kill more cancer cells in patients undergoing donor stem cell transplantation.
PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients with advanced acute myeloid
leukemia or acute lymphoblastic leukemia.
Condition
|
Treatment or Intervention |
Phase |
adult acute lymphoblastic leukemia adult acute myeloid leukemia childhood acute lymphoblastic leukemia childhood acute myeloid leukemia and other myeloid malignancies secondary acute myeloid leukemia
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Drug: allogeneic lymphocytes Drug: interleukin-2 Procedure: allogeneic bone marrow transplantation Procedure: biological response modifier therapy Procedure: bone marrow ablation with stem cell support Procedure: bone marrow transplantation Procedure: cytokine therapy Procedure: interleukin therapy Procedure: leukocyte therapy Procedure: peripheral blood lymphocyte therapy Procedure: peripheral blood stem cell transplantation
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Phase I Phase II
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MedlinePlus related topics: Bone Marrow Diseases; Immune System and Disorders; Leukemia, Adult Acute; Leukemia, Adult Chronic; Leukemia, Childhood; Lymphatic Diseases
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Pilot Study of Adoptive Immunotherapy Comprising CD8-Positive Wilms' Tumor (WT1) Gene-Specific Cytotoxic T-Lymphocyte
Clones and Interleukin-2 in Patients With HLA-A2 or HLA-A24-Positive Advanced Acute Myeloid Leukemia or Acute Lymphoblastic
Leukemia At High Risk for Relapse After Allogeneic Stem Cell Transplantation
Further Study Details:
OBJECTIVES:
- Determine the safety and potential toxic effects of adoptive immunotherapy comprising CD8-positive Wilms' tumor (WT1) gene-specific
cytotoxic T-lymphocyte (CTL) clones and interleukin-2 in patients with HLA-A2 or HLA-A24-positive advanced acute myeloid leukemia
or acute lymphoblastic leukemia at high risk for relapse after allogeneic stem cell transplantation.
- Determine the in vivo persistence of this therapy and assess migration to the bone marrow in these patients.
- Determine the anti-leukemic effects of this therapy in these patients.
OUTLINE: Donors undergo leukapheresis or peripheral blood draw for stem cell harvest to generate CD8-positive Wilms' tumor
(WT1) gene-specific cytotoxic T-lymphocyte (CTL) clones before allogeneic stem cell transplantation.
After post-transplantation hematopoietic recovery, patients receive treatment for either highest-risk disease (prophylactically)
or relapsed disease.
- Highest-risk disease group: Patients receive CD8-positive Wilms' tumor (WT1) gene-specific CTL clones IV over 1-2 hours on
days 0, 7, 14, 28, and 49. Patients receive interleukin-2 subcutaneously twice daily on days 28-41 and 49-62 in the absence
of unacceptable toxicity.
- Relapsed-disease group: Some patients with morphologic evidence of leukemic relapse may receive standard salvage chemotherapy
prior to donor CTL infusions and then receive CD8-positive Wilms' tumor (WT1) gene-specific CTL clones and interleukin-2 as
in the highest-risk group. Patients in both groups who have progressive disease after study may be eligible for retreatment
with CD8-positive Wilms' tumor (WT1) gene-specific CTL clones.
Patients are followed until day 90, at day 180, and then every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 15-35 patients will be accrued for this study within 3-5 years.
Eligibility
Ages Eligible for Study:
up to 75 Years,
Genders Eligible for Study:
Both
DISEASE CHARACTERISTICS:
- Planned allogeneic stem cell transplantation for one of the following diagnoses:
- Primary refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL)
- AML or ALL beyond first remission
- Therapy-related AML at any stage
- Philadelphia chromosome-positive ALL at any stage
- Acute leukemia at any stage arising from myelodysplastic or myeloproliferative syndromes, including:
- Chronic myelomonocytic leukemia
- Chronic myelogenous leukemia
- Polycythemia vera
- Essential thrombocytosis
- Agnogenic myeloid metaplasia with myelofibrosis
- Patient and donor must be HLA-A2 or HLA-A24 positive
- Evidence of Wilms' tumor (WT1) gene overexpression by polymerase chain reaction (PCR)
- No grade III or IV graft-versus-host disease unresponsive to therapy or requiring therapy with any of the following:
- Prednisone
- Anti-CD3 monoclonal antibody
- Other treatments resulting in T-cell inactivation or ablation
- No graft rejection or failure
- Highest-risk disease group: More than 5% blasts detected in bone marrow or peripheral blood just prior to or at time of transplantation
- One of the following types of relapsed disease after transplantation:
- Morphologic relapse defined by one or more of the following:
- Peripheral blasts in absence of growth factor therapy
- Bone marrow blasts more than 5% of nucleated cells
- Extramedullary chloroma or granulocytic sarcoma
- Cells with abnormal immunophenotype and consistent with leukemia relapse in the peripheral blood or bone marrow detected by
flow cytometry
- Cytogenetic relapse defined as the appearance in 1 or more metaphases from peripheral blood or bone marrow of either a non-constitutional
cytogenetic abnormality identified in at least 1 cytogenetic study performed before transplantation or a new abnormality known
to be associated with leukemia
- Molecular relapse defined as one of the following:
- 1 or more positive PCR assays for clonotypic immunoglobulin heavy chain (IgH) gene rearrangement for patients with B-cell
ALL
- 1 or more positive PCR assays for T-cell receptor (TCR) gene rearrangement for patients with T-cell ALL
- 1 or more positive post-transplantation reverse transcription PCR assays for bcr-abl mRNA fusion transcripts in patients with
bcr-abl-positive ALL
PATIENT CHARACTERISTICS: Age
Performance status
- Karnofsky 40-100% OR
- Lansky 40-100%
Life expectancy
Hematopoietic
- See Disease Characteristics
- Absolute neutrophil count greater than 500/mm^3 for at least 7 days prior to study (highest-risk group)
Hepatic
Renal
Other
- Not pregnant
- Fertile patients must use effective contraception
- No pre-existing nonhematopoietic organ toxicity greater than grade 2
PRIOR CONCURRENT THERAPY: Biologic therapy
- See Disease Characteristics
Chemotherapy
Endocrine therapy
- See Disease Characteristics
- Concurrent immunosuppressive therapy for graft-versus-host disease (GVHD) allowed if meets 1 of the following criteria:
- Not receiving corticosteroids
- Corticosteroid dose can be tapered no more than 0.5 mg/kg/day without an increase to grade III or IV acute GVHD or progression
of chronic GVHD within 14 days of dose change
Radiotherapy
Surgery
Location
Information
Study chairs or principal investigators
William Y. Ho, MD, Study Chair, Fred Hutchinson Cancer Research Center
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers:
CDR0000258507; FHCRC-1655.00
Record last reviewed:
January 2004
Record first received:
January 24, 2003
ClinicalTrials.gov Identifier:
NCT00052520Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20