April 5, 2005 |
September 16, 2010 |
December 1998 |
August 2009 (final data collection date for primary outcome measure) |
Toxicity [ Designated as safety issue: Yes ] |
Toxicity |
Complete list of historical versions of study NCT00107354 on ClinicalTrials.gov Archive Site |
- In vivo persistence of adoptively transferred T cells [ Designated as safety issue: No ]
- Migration of adoptively transferred T cells to the bone marrow [ Designated as safety issue: No ]
- Antileukemic activity [ Designated as safety issue: No ]
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- In vivo persistence of adoptively transferred T cells
- Migration of adoptively transferred T cells to the bone marrow
- Antileukemic activity
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Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant |
Phase I Study of Adoptive Immunotherapy With CD8 Minor Histocompatibility (H) Antigen-Specific CTL Clones for Patients With Relapsed of AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant |
RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop cancer cells from growing.
PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after donor stem cell transplant. |
OBJECTIVES:
Primary
- Determine the toxic effects of adoptive immunotherapy comprising CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes that relapsed after allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the persistence of adoptively transfused T cells in vivo and assess their migration to the bone marrow in these patients.
- Determine the anti-leukemic activity of this therapy in these patients.
OUTLINE: This is a pilot, open-label, nonrandomized study.
- Leukapheresis: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) before transplantation. Donors undergo leukapheresis to obtain PBMCs to use as feeder cells for generating adoptive immunotherapy. Patient PBMCs are combined with donor PBMCs and expanded in vitro to generate CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes (CTLs) for adoptive immunotherapy.
- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation. Patients with a morphologic or flow cytometric relapse on or after day 100 post-transplantation proceed to cytoreductive chemotherapy. Patients with a molecular or cytogenetic relapse on or after day 100 post-transplantation proceed directly to adoptive immunotherapy. Patients with relapsed disease before day 100 post-transplantation are eligible to receive adoptive immunotherapy at a later date provided the patient continues to relapse and CTLs are available.
Cytoreductive chemotherapy: The chemotherapy regimen for each patient is determined after consideration of prior chemotherapy, type of leukemia, and other clinical parameters. Two regimens to consider are:
- Mitoxantrone IV and etoposide IV on days -6 to -2
- High-dose cytarabine IV over 2 hours twice daily on days -6, -4, and -2 Patients achieving a complete remission after completion of cytoreductive chemotherapy proceed to adoptive immunotherapy.
- Adoptive immunotherapy: Within 2-3 days after completion of cytoreductive chemotherapy, patients receive CTLs IV over 1-2 hours on days 0, 4, 11, 21, and 28 in the absence of unacceptable toxicity. Patients with evidence of persistent disease on or after day 35 OR relapsed disease after an initial response to CTLs receive a sixth infusion of CTLs followed, no more than 24 hours later, by interleukin-2 subcutaneously once daily for up 14 total doses in the absence of unacceptable toxicity. Patients with subsequent relapsed disease after day 48 may be eligible for retreatment.
After completion of study treatment, patients are followed with bone marrow aspiration every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 25-30 patients (10-15 with acute myeloid leukemia or myelodysplastic syndromes AND 10-15 with acute lymphoblastic leukemia) will be accrued for this study within 3 years. |
Interventional |
Phase 1 |
Masking: Open Label Primary Purpose: Treatment |
- Leukemia
- Myelodysplastic Syndromes
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- Biological: aldesleukin
- Biological: therapeutic allogeneic lymphocytes
- Biological: therapeutic autologous lymphocytes
- Drug: cytarabine
- Drug: etoposide
- Drug: mitoxantrone hydrochloride
- Procedure: allogeneic bone marrow transplantation
- Procedure: peripheral blood stem cell transplantation
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- Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood. 2010 May 13;115(19):3869-78. Epub 2010 Jan 13.
- Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Blood. 2008 May 1;111(9):4817-26. Epub 2008 Feb 25.
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Completed |
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August 2009 (final data collection date for primary outcome measure) |
DISEASE CHARACTERISTICS:
Undergoing allogeneic hematopoietic stem cell transplantation* from a major histocompatability complex (MHC)-identical related donor for 1 of the following:
Relapsed disease post-transplantation, as evidenced by 1 of the following criteria:
Morphologic relapse, as defined by 1 or more of the following:
- Peripheral blasts in the absence of growth factor therapy
- Bone marrow blasts > 5% of nucleated cells
- Extramedullary chloroma or granulocytic sarcoma
- Flow cytometric relapse, as defined by the appearance of cells with abnormal immunophenotype consistent with leukemia relapse in the peripheral blood or bone marrow (detected before transplantation)
- Cytogenetic relapse, as defined by the appearance in 1 or more metaphases from bone marrow or peripheral blood cells of either a non-constitutional cytogenetic abnormality detected in at least 1 cytogenetic study performed before transplantation OR a new abnormality known to be associated with leukemia
Molecular relapse, as defined by 1 of the following:
- 1 or more positive polymerase chain reaction (PCR) assays for clonotypic immunoglobulin heavy chain or T-cell receptor gene rearrangement in patients transplanted for B- or T-cell ALL respectively
- 1 or more positive post-transplantation reverse transcription PCR assays for p190 BCR-ABL mRNA fusion transcripts in patients transplanted for Philadelphia chromosome-positive p190-positive ALL
- No grade III or IV acute graft-versus-host disease (GVHD)**
- No extensive chronic GVHD** NOTE: **At time of post-transplant relapse
PATIENT CHARACTERISTICS:
Age
- 14 and over (patients < 14 years of age may be eligible if they are deemed to be of sufficient height and weight by the pediatric attending physician)
Performance status
- Karnofsky 60-100% (at time of post-transplant relapse)
Life expectancy
Hematopoietic
Hepatic
Renal
Other
- No preexisting major nonhematopoietic organ toxicity ≥ grade 3 (at time of post-transplant relapse)
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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Both |
14 Years and older |
No |
Contact information is only displayed when the study is recruiting subjects |
United States |
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NCT00107354 |
1334.00, CDR0000407784 |
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Fred Hutchinson Cancer Research Center |
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Principal Investigator: |
Edus H. Warren, MD, PhD |
Fred Hutchinson Cancer Research Center |
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Fred Hutchinson Cancer Research Center |
September 2010 |