Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant
NCT ID: NCT00107354
Last Updated: 2010-09-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
INTERVENTIONAL
1998-12-31
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Study Design
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TREATMENT
NONE
Interventions
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aldesleukin
therapeutic allogeneic lymphocytes
therapeutic autologous lymphocytes
cytarabine
etoposide
mitoxantrone hydrochloride
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
Eligibility Criteria
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Inclusion Criteria
* Karnofsky 60-100% (at time of post-transplant relapse)
Life expectancy
* Not specified
Hematopoietic
* Not specified
Hepatic
* Not specified
Renal
* Not specified
Other
* No preexisting major nonhematopoietic organ toxicity ≥ grade 3 (at time of post-transplant relapse)
PRIOR CONCURRENT THERAPY:
Biologic therapy
* Not specified
Chemotherapy
* Not specified
Endocrine therapy
* Concurrent immunosuppressive steroid therapy for GVHD allowed provided both of the following are true:
* Able to taper steroid dose to \< 0.5 mg/kg/day
* No increase of \> 1 grade in acute GVHD OR progression of chronic GVHD within 14 days after dose change
Radiotherapy
* Not specified
Surgery
* Not specified
14 Years
ALL
No
Sponsors
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Fred Hutchinson Cancer Center
OTHER
Principal Investigators
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Edus H. Warren, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Fred Hutchinson Cancer Center
Locations
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Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Countries
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References
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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. doi: 10.1182/blood-2009-10-248997. 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. doi: 10.1182/blood-2007-06-096313. Epub 2008 Feb 25.
Other Identifiers
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CDR0000407784
Identifier Type: -
Identifier Source: secondary_id
1334.00
Identifier Type: -
Identifier Source: org_study_id