Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant
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|ClinicalTrials.gov Identifier: NCT00107354|
Recruitment Status : Completed
First Posted : April 6, 2005
Last Update Posted : September 20, 2010
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes||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||Phase 1|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||December 1998|
|Actual Primary Completion Date :||August 2009|
- In vivo persistence of adoptively transferred T cells
- Migration of adoptively transferred T cells to the bone marrow
- Antileukemic activity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00107354
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Principal Investigator:||Edus H. Warren, MD, PhD||Fred Hutchinson Cancer Research Center|