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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.
Verified November 2017 by Fred Hutchinson Cancer Research Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01640301
First Posted: July 13, 2012
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
  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 acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) that has returned after a period of improvement (relapsed), 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
Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Therapy-Related Acute Myeloid Leukemia Biological: Aldesleukin Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Biological: WT1-Sensitized Allogeneic T-Lymphocytes Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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 Relapsed AML

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Anti-leukemic potential efficacy, in terms of duration of response (Arm II) [ Time Frame: Up to 15 years ]
    Will be observed.

  • Efficacy, in terms of relapse rate (Arm I) [ Time Frame: At 1 year post-transplant ]
    Will be observed.

  • Incidence of chronic graft versus host disease (GVHD) (Arm I) [ Time Frame: Up to 15 years ]
    Will be observed.

  • Incidence of chronic graft versus host disease (GVHD) (Arm II) [ Time Frame: Up to 15 years ]
    Will be observed.

  • Incidence of grade III-IV acute graft versus host disease (GVHD) (Arm II) [ Time Frame: Up to 15 years ]
    Will be observed.

  • Incidence of grade III-IV acute graft-versus-host disease (GVHD) (Arm I) [ Time Frame: Up to 15 years ]
    Will be observed.

  • Treatment-related toxicity rate (Arm I) [ Time Frame: Up to 15 years ]
    Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

  • Treatment-related toxicity rate (Arm II) [ Time Frame: Up to 15 years ]
    Will be graded according to the NCI CTCAE 4.0.


Secondary Outcome Measures:
  • Disease-free survival after T cell therapy [ Time Frame: Up to 15 years ]
    Will be observed.

  • Incidence of relapse after T cell therapy [ Time Frame: Up to 15 years ]
    Will be observed.

  • Maintenance of T cell receptor (TCR) expression and function of transduced T cells [ Time Frame: Up to 15 years ]
    Will be observed.

  • Persistence and migration of transferred T cells to bone marrow [ Time Frame: Up to 3-5 days after aldesleukin has been completed ]
    Will be observed.

  • Time to progression after T cell therapy [ Time Frame: Up to 15 years ]
    Will be observed.


Estimated Enrollment: 55
Actual Study Start Date: December 6, 2012
Estimated Study Completion Date: October 1, 2030
Estimated Primary Completion Date: October 1, 2020 (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 leukemia or MDS post-HCT receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin SC BID on days 14-28.
Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: WT1-Sensitized Allogeneic T-Lymphocytes
Given IV
Experimental: Arm II (relapsed after HCT)
Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.
Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: WT1-Sensitized Allogeneic T-Lymphocytes
Given IV

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).

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 leukemia post-HCT receive WT1-sensitized T cells intravenously (IV) over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28.

ARM II: Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.

After completion of study treatment, patients are followed up weekly for 4 weeks, at weeks 6 and 8, at 3, 6, 12 months, and then annually for up to 15 years.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must express HLA-A*0201
  • Patients who are currently undergoing or who previously underwent matched allogeneic HCT for:

    • AML: Prospective enrollment will now be limited to patients with relapsed disease (overt relapse or minimal residual disease) at any time post allogeneic HCT
    • MDS will no longer be a criterion for eligibility
    • CML will no longer be a criterion for eligibility
  • 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 >= 15 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; testing for HIV should be within 6 months of enrollment
  • 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 (B-hCG) pregnancy test result within 14 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
Information from the National Library of Medicine

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): NCT01640301


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Daniel Egan    206-667-4971    degan@fredhutch.org   
Principal Investigator: Daniel Egan         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Daniel Egan Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01640301     History of Changes
Other Study ID Numbers: 2498.00
NCI-2011-03362 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2498
2498.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P01CA018029 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: November 29, 2011
First Posted: July 13, 2012
Last Update Posted: November 7, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents