Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant

NCT00107354 | Completed Phase 1

• 2 other identifiers: 1334.00CDR0000407784
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; T-cell adult acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia; B-cell adult acute lymphoblastic leukemia; B-cell childhood acute lymphoblastic leukemia; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Toxicity

Secondary Outcomes (3)

• In vivo persistence of adoptively transferred T cells

• Migration of adoptively transferred T cells to the bone marrow

• Antileukemic activity

Interventions

aldesleukin BIOLOGICAL

therapeutic allogeneic lymphocytes BIOLOGICAL

therapeutic autologous lymphocytes BIOLOGICAL

cytarabine DRUG

etoposide DRUG

mitoxantrone hydrochloride DRUG

allogeneic bone marrow transplantation PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Undergoing allogeneic hematopoietic stem cell transplantation\* from a major histocompatability complex (MHC)-identical related donor for 1 of the following: * Primary refractory acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) * AML or ALL beyond first remission * Therapy-related AML at any stage * Philadelphia chromosome (bcr-abl)-positive p190-positive ALL at any stage * Acute leukemia at any stage arising from myelodysplastic syndromes or myeloproliferative disorders, including any of the following: * Chronic myelomonocytic leukemia * Chronic myelogenous leukemia * Polycythemia vera * Essential thrombocytosis * Agnogenic myeloid metaplasia with myelofibrosis * Refractory anemia with excess blasts * Refractory anemia with excess blasts in transformation NOTE: \*Patients must be enrolled on study prior to undergoing transplantation * 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 * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Related Publications (2)

• 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.

  PMID: 20071660 DERIVED

• 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.

  PMID: 18299450 DERIVED

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts; Congenital Abnormalities

Interventions

aldesleukin; Cytarabine; Etoposide; Mitoxantrone; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Anemia, Refractory; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Edus H. Warren, MD, PhD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 5, 2005
• First Posted: April 6, 2005
• Study Start: December 1, 1998
• Primary Completion: August 1, 2009
• Last Updated: September 20, 2010

Record last verified: 2010-09

Locations

US (1)