Clinical Trials /

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

NCT01640301

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2498.00
  • SECONDARY ID: NCI-2011-03362
  • SECONDARY ID: 2498
  • SECONDARY ID: 2498.00
  • SECONDARY ID: P01CA018029
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT01640301

Conditions

  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Aldesleukin125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2Arm I (high-risk for relapse after HCT)
Cyclophosphamide(-)-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- 138719Arm II (relapsed after HCT)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Arm II (relapsed after HCT)
WT1-Sensitized Allogeneic T-LymphocytesArm I (high-risk for relapse after HCT)

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (high-risk for relapse after HCT)ExperimentalPatients 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.
  • Aldesleukin
  • WT1-Sensitized Allogeneic T-Lymphocytes
Arm II (relapsed after HCT)ExperimentalPatients 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.
  • Aldesleukin
  • Cyclophosphamide
  • Fludarabine Phosphate
  • WT1-Sensitized Allogeneic T-Lymphocytes

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Anti-leukemic potential efficacy, in terms of duration of response (Arm II)
Time Frame:Up to 15 years
Safety Issue:
Description:Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

Secondary Outcome Measures

Measure:Disease-free survival after T cell therapy
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Incidence of relapse after T cell therapy
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Maintenance of T cell receptor (TCR) expression and function of transduced T cells
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Persistence and migration of transferred T cells to bone marrow
Time Frame:Up to 3-5 days after aldesleukin has been completed
Safety Issue:
Description:
Measure:Time to progression after T cell therapy
Time Frame:Up to 15 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

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