RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop cancer cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining cellular adoptive immunotherapy with interleukin-2 may be effective treatment for recurrent accelerated or blast phase chronic myelogenous leukemia.

PURPOSE: Phase I/II trial to study the effectiveness of combining cellular adoptive immunotherapy with interleukin-2 in treating patients who have recurrent accelerated or blast phase chronic myelogenous leukemia after undergoing allogeneic stem cell transplantation.

Condition	Treatment or Intervention	Phase
accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia childhood chronic myelogenous leukemia	Drug: allogeneic lymphocytes  Drug: interleukin-2  Procedure: adjuvant therapy  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	Phase I Phase II

OBJECTIVES:

• Determine the safety and potential toxic effects of adoptive immunotherapy comprising CD8+ proteinase 3 (PR3)-specific cytotoxic T-lymphocyte (CTL) clones and interleukin-2 in patients with recurrent accelerated or blastic phase chronic myelogenous leukemia after allogeneic stem cell transplantation.
• Determine the in vivo persistence of this therapy and assess migration to bone marrow in these patients.
• Determine the antileukemic activity of this therapy in these patients.

OUTLINE: This is an open-label, non-randomized, pilot study.

Donors undergo leukapheresis for the harvest of allogeneic blood mononuclear cells. CD8+ proteinase 3 (PR3)-specific cytotoxic T-lymphocytes (CTLs) are isolated as clones and generated ex vivo.

Patients undergo allogeneic stem cell transplantation.

Patients with relapse/progression (more than 5% leukemic blasts in marrow) after transplantation may receive cytoreductive chemotherapy before adoptive immunotherapy.

After leukemic relapse or progression, patients receive adoptive immunotherapy comprising allogeneic CD8+ PR3-specific CTLs IV over 1-2 hours on days 0, 7, 14, 28, and 49 and interleukin-2 subcutaneously twice daily on days 28-41 and 49-62. Treatment continues in the absence of unacceptable toxicity.

Patients with disease progression or recurrence after adoptive immunotherapy may be eligible to repeat treatment.

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.

Ages Eligible for Study:  up to  75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of accelerated or blastic phase chronic myelogenous leukemia
• Undergoing allogeneic stem cell transplantation
• Patient and donor must be HLA-A2 positive
• Evidence of proteinase 3 (PR3) expression by immunohistochemistry or flow cytometry
• Able and willing to provide blood and bone marrow samples for study
• Evidence of recurrent or progressive disease post-transplantation
• Morphologic relapse defined as at least 1 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
• Flow cytometric relapse
• Cells with abnormal immunophenotype in the peripheral blood or bone marrow by flow cytometry and consistent with leukemia relapse or progression
• Cytogenetic relapse or progression
• Increase in the number of Philadelphia chromosome-positive metaphases from bone marrow or peripheral blood between 2 consecutive samples after engraftment
• Increase in the percentage of bcr/abl+ cells by fluorescence in situ hybridization between 2 consecutive samples after engraftment
• Molecular relapse or progression
• Polymerase chain reaction assay of bone marrow or peripheral blood mononuclear cells positive for the presence of the bcr/abl mRNA fusion transcript that quantitatively increases by greater than 1 order of magnitude on a subsequent sample
• No grade III or IV graft-versus-host disease unresponsive to therapy or requiring treatment with any of the following:
• Anti-CD3 monoclonal antibody
• Prednisone (or equivalent) more than 0.5 mg/kg/day
• Other treatments resulting in the ablation or inactivation of T cells (e.g., anti-T-cell monoclonal antibodies)
• No graft rejection or failure

PATIENT CHARACTERISTICS: Age

• 75 and under

Performance status

• Karnofsky 40-100% OR
• Lansky 40-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Not specified

Renal

• Not specified

Other

• No grade 3 or 4 nonhematopoietic organ toxicity
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

• No concurrent hydroxyurea

Endocrine therapy

• See Disease Characteristics
• Concurrent immunosuppressive therapy for graft-versus-host disease (GVHD) allowed if 1 of the following:
• 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

• Not specified

Surgery

• Not specified

Other

• No concurrent agents that may interfere with function or survival of infused cytotoxic T-lymphocyte clones

Study chairs or principal investigators

William Y. Ho, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000258557; FHCRC-1671.00
Record last reviewed:  January 2004
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052598
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20