Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01640301
First received: November 29, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) previously treated with donor stem cell transplant. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Placing a gene that has been created in the laboratory into a person's T cells may make the body build an immune response to kill cancer cells.


Condition Intervention Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Chronic Phase Chronic Myelogenous Leukemia
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Biological: WT1-sensitized T cells
Biological: aldesleukin
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Adoptive Immunotherapy After Allogeneic HCT With Virus Specific CD8+ T Cells That Have Been Transduced to Express a WT1-specific T Cell Receptor for Patients With High Risk or Relapsed AML, MDS, or CML

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Toxicity rate associated with infusing WT1-sensitized T cells in patients at high risk for post-transplant AML, MDS or CML relapse, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0 (Arm I) [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
  • Anti-leukemic activity and potential toxicities of WT1-sensitized T cells in patients with relapsed AML, MDS or CML post-transplant, graded according to the NCI CTCAE version 4 (Arm II) [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
  • Disease response when treating patients with active disease (minimal residual or overt disease) [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Persistence and migration of transferred T cells to bone marrow [ Time Frame: Up to 3-5 days after IL2 has been completed ] [ Designated as safety issue: No ]
  • Maintenance of TCR expression and function of transduced T cells [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Disease-free survival after T cell therapy [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Incidence of relapse after T cell therapy [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Time to progression after T cell therapy [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: December 2012
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (high-risk for relapse after HCT)
Patients with no evidence of disease post-HCT receive WT1-sensitized T cells IV over 1-2 hours on days 0 and 14 and aldesleukin SC BID on days 14-28.
Biological: WT1-sensitized T cells
Given IV
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (relapsed after HCT)
Patients with minimal residual disease or overt disease post-HCT receive WT1-sensitized T cells IV over 1-2 hours on days 0 and 14 and aldesleukin SC BID on days 14-28.
Biological: WT1-sensitized T cells
Given IV
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and potential toxicities associated with treating patients with high risk or relapsed AML, MDS and CML after allogeneic hematopoietic cell transplantation (HCT) by adoptive transfer of virus-specific cluster of differentiation (CD)8 T cells genetically-modified to express a high affinity Wilms tumor 1 (WT1)-specific T cell receptor (TCR) (WT1-sensitized T cells).

II. Determine the anti-leukemic activity associated with treating patients with relapsed AML, MDS and CML after allogeneic HCT by adoptive transfer of virus-specific CD8 T cells genetically-modified to express a high affinity WT1-specific T cell receptor (TCR).

SECONDARY OBJECTIVES:

I. Determine the in vivo persistence of transferred T cells and ability to migrate to and accumulate in bone marrow.

II. Determine the maintenance of TCR expression and function of transduced T cells.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients with no evidence of disease post-HCT receive WT1-sensitized T cells intravenously (IV) over 1-2 hours on days 0 and 14 and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28.

ARM II: Patients with minimal residual disease or overt disease post-HCT receive WT1-sensitized T cells IV over 1-2 hours on days 0 and 14 and aldesleukin SC BID on days 14-28.

After completion of study treatment, patients are followed up at 3, 6, 12 months, and then annually for up to 15 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must express human leukocyte antigen (HLA)-A*0201
  • Patients who are currently undergoing or who previously underwent matched allogeneic hematopoietic cell transplantation (HCT) for:
  • A) AML including:

    • AML beyond first remission, therapy-related AML at any stage, primary refractory AML, AML in relapse (before or after HCT), AML with evidence of minimal residual disease (MRD) at time of HCT or after HCT (by multiparameter flow cytometry, cytogenetics, fluorescence in situ hybridization [FISH] or molecular studies); AML at any stage arising in a patient with an antecedent diagnosis of a hematologic disorder including myelodysplastic or myeloproliferative syndrome (e.g. chronic myelomonocytic leukemia, polycythemia vera, essential thrombocytosis, and agnogenic myeloid metaplasia with myelofibrosis)
    • AML at any stage with unfavorable cytogenetic, FISH, or molecular abnormalities:

      • Monosomal karyotype (presence of two or more distinct autosomal chromosome monosomies or a single autosomal monosomy associated with at least one structural abnormality)
      • del(5q)/-5
      • -7/del(7q)
      • abn 3q
      • abn 9q
      • abn 11q
      • abn 20q
      • abn 21q
      • abn 17p
      • t(6;9)
      • t(9;22)
      • Complex karyotype (>= 3 unrelated abnormalities)
      • Inv(3) or t(3;3)
      • t(6;11)
      • +8 sol
      • +8 with 1 other abnormality/ies other than t(8;21), t(9;11), inv (16), t(16;16), t(15;17)
      • Fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation
      • Other cytogenetics, FISH or molecular abnormalities per discussion and approval by patient care conference (PCC)
    • Relapsed disease (overt relapse or minimal residual disease) at any time post HCT
    • Other clinical manifestations consistent with high risk disease per discussion and approval by PCC
  • B) MDS including:

    • Intermediate-2 or high risk category patients according to the International Prognostic Scoring System (IPSS >= 1.5) or poor risk karyotype defined as abnormalities involving chromosome 7 or complex karyotype (>= 3 unrelated abnormalities)
    • Relapsed disease (overt relapse or minimal residual disease) at any time post HCT
    • Other clinical manifestations consistent with high risk disease per discussion and approval by PCC
  • C) CML including:

    • CML beyond chronic phase
    • Relapsed disease (overt relapse or minimal residual disease) at any time post-HCT
    • Other clinical manifestations consistent with high risk disease per discussion and approval by PCC
  • Patients must have an HLA-matched donor of hematopoietic stem cells (related or unrelated)
  • Patients must be able to provide blood and bone marrow samples and undergo the procedures required for this protocol
  • Patients must be >= 50 kg
  • Patients must be able to give informed consent; parent or legal representative will be asked to consent for patients younger than 18 year old
  • DONOR: Patient and donor (related or unrelated) must be HLA-matched and express HLA-A*0201
  • DONOR: Donor must be Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositive
  • DONOR: Donor must be age 18 or older
  • DONOR: In good general health
  • DONOR: Able to give informed consent

Exclusion Criteria:

  • Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or cranio-spinal radiation
  • In patients whose leukemic cells are available for evaluation, the expression of WT1 in the patient's bone marrow will be determined; if WT1 expression in the patient's bone marrow is not highly expressed by polymerase chain reaction (PCR), the patient will be excluded from the study; patients with no evaluable leukemia will be eligible for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia will be evaluated for WT1 expression if recurrence is detected
  • Human immunodeficiency virus (HIV) seropositive
  • Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)
  • Pregnancy or breast-feeding; women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test result within 7 days before the first dose of WT1-specific T cell infusion; woman of non-childbearing potential will be defined as being postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy; all recipients of WT1-specific T cells will be counseled to use effective birth control during participation in this study and for 12 months after the last T cell infusion
  • DONOR: Less than 18 years old
  • DONOR: Active infectious hepatitis
  • DONOR: HIV or human T-lymphotropic virus (HTLV) seropositive
  • DONOR: Pregnancy or nursing
  • DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make the donor an unsuitable T cell donor
  • DONOR: Unable to give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01640301

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Merav Bar    206-667-4971      
Principal Investigator: Merav Bar         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Merav Bar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01640301     History of Changes
Other Study ID Numbers: 2498.00, NCI-2011-03362, 2498.00, P30CA015704, P01CA018029
Study First Received: November 29, 2011
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 20, 2014