Clinical Trials /

Genetically Modified Therapeutic Autologous Lymphocytes Followed by Aldesleukin in Treating Patients With Stage III or Metastatic Melanoma

NCT01740557

Description:

This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Genetically Modified Therapeutic Autologous Lymphocytes Followed by Aldesleukin in Treating Patients With Stage III or Metastatic Melanoma
  • Official Title: A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With T -Cells Transduced With CXCR2 and NGFR Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 2009-0471
  • SECONDARY ID: NCI-2014-02655
  • SECONDARY ID: 2009-0471
  • SECONDARY ID: P30CA016672
  • SECONDARY ID: R01CA116206
  • NCT ID: NCT01740557

Conditions

  • Metastatic Melanoma
  • Stage III Cutaneous Melanoma AJCC v7
  • Stage IV Cutaneous Melanoma AJCC v6 and v7

Interventions

DrugSynonymsArms
Aldesleukin125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2Treatment (genetically modified T-cells, high-dose aldesleukin
CXCR2-transduced Autologous Tumor Infiltrating LymphocytesCXCR2-transduced Autologous TILsTreatment (genetically modified T-cells, high-dose aldesleukin
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- 138719Treatment (genetically modified T-cells, high-dose aldesleukin
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (genetically modified T-cells, high-dose aldesleukin
NGFR-transduced Autologous T LymphocytesTreatment (genetically modified T-cells, high-dose aldesleukin

Purpose

This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the feasibility and safety of CXCR2 and NGFR transduced tumor-infiltrating
      lymphocytes (TIL) for treating metastatic malignant melanoma.

      SECONDARY OBJECTIVES:

      I. Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma
      tumors.

      II. Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess
      whether this correlates with the tumor localization of CXCR2 transduced TIL.

      III. Characterize the clinical response and correlate with migration of CXCR2 transduced TIL
      to the tumor and levels of CXCL1 and CXCL8 at the tumor site.

      OUTLINE:

      Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6,
      fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced
      autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients
      then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15
      doses) and 22-26 (up to 15 doses).

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (genetically modified T-cells, high-dose aldesleukinExperimentalPatients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).
  • Aldesleukin
  • CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes
  • Cyclophosphamide
  • Fludarabine Phosphate
  • NGFR-transduced Autologous T Lymphocytes

Eligibility Criteria

        Inclusion Criteria:

          -  TURNSTILE I INCLUSION CRITERIA:

          -  Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or
             regional nodal disease (Turnstile I)

          -  Patients must have a lesion amenable to resection for the generation of TIL (Turnstile
             I)

          -  Patients must receive a magnetic resonance imaging (MRI)/computed tomography
             (CT)/positron emission tomography (PET) of the brain within 6 months of signing
             informed consent; if new lesions are present, patient must have definitive treatment;
             principal investigator (PI) or his designee should make final determination regarding
             enrollment (Turnstile I)

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 within 30
             days of signing informed consent (Turnstile I)

          -  Patients previously treated with immunotherapy, targeted therapy, or no therapy will
             be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his
             designee

          -  Patients with a negative pregnancy test (urine or serum) must be documented within 14
             days of screening for women of childbearing potential (WOCBP); a WOCBP has not
             undergone a hysterectomy or who has not been naturally postmenopausal for at least 12
             consecutive months (Turnstile I)

          -  CHEMOTHERAPY/CELL INFUSION INCLUSION CRITERIA:

          -  Patients must have adequate TIL available (Turnstile II)

          -  Patients must have at least one biopsiable and measurable metastatic melanoma lesions
             >= 1 cm (Turnstile II)

          -  Patients may have brain lesions which measure =< 1 cm each (Turnstile II)

          -  Patients of both genders must practice birth control for four months after receiving
             the preparative regimen (lymphodepletion) and continue to practice birth control
             throughout the study; patients must have a documented negative pregnancy test (urine
             or serum) for women who have menstruation in the past 12 months and without
             sterilization surgery (Turnstile II)

          -  Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the
             patient agrees to continue to use a barrier method of contraception throughout the
             study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus
             spermicide; abstinence is an acceptable form of birth control (Turnstile II)

          -  Pregnancy testing will be performed within 14 days prior to treatment (Turnstile II)

          -  Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (Turnstile
             II)

          -  Absolute neutrophil count greater than or equal to 1000/mm^3 (Turnstile II)

          -  Platelet count greater than or equal to 100,000/mm^3 (Turnstile II)

          -  Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II)

          -  Serum alanine transaminase (ALT) less than three times the upper limit of normal
             (Turnstile II)

          -  Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II)

          -  Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's
             syndrome who must have a total bilirubin less than 3.0 mg/dl (Turnstile II)

          -  A stress cardiac test (stress thallium, stress multigated acquisition [MUGA] scan,
             dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
             within 6 months of lymphodepletion (Turnstile II)

          -  Forced expiratory volume in 1 second (FEV1) > 65% of predicted within 6 months of
             lymphodepletion (Turnstile II) or

          -  Forced vital capacity (FVC) > 65% of predicted within 6 months of lymphodepletion
             (Turnstile II)

          -  MRI/CT/PET of the brain within 30 days of lymphodepletion

        Exclusion Criteria:

          -  Active systemic infections requiring intravenous antibiotics, coagulation disorders or
             other major medical illnesses of the cardiovascular, respiratory or immune system; PI
             or his designee shall make the final determination regarding appropriateness of
             enrollment (Turnstile I)

          -  Patients who are pregnant or nursing (Turnstile I)

          -  CHEMOTHERAPY/CELL INFUSION EXCLUSION CRITERIA:

          -  Has had prior systemic cancer therapy within the past four weeks at the time of the
             start of the lymphodepletion regimen (Turnstile II)

          -  Women who are pregnant will be excluded (Turnstile II)

          -  Any active systemic infections requiring intravenous antibiotics, coagulation
             disorders or other major medical illnesses of the cardiovascular, respiratory or
             immune system, such as abnormal stress thallium or comparable test, myocardial
             infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease; PI or
             his designee shall make the final determination regarding appropriateness of
             enrollment (Turnstile II)

          -  Any form of primary or secondary immunodeficiency; must have recovered immune
             competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts
             (> 500/mm^3), white blood cell (WBC) (> 3,000/mm^3) or absence of opportunistic
             infections (Turnstile II)

          -  Requires no steroids within 4 weeks and have not used topical or inhalational steroids
             in the past 2 weeks prior to lymphodepletion; the exception being patients on chronic
             physiologic dose of steroid (Turnstile II)

          -  Presence of a significant psychiatric disease, which in the opinion of the principal
             investigator or his designee, would prevent adequate informed consent or render
             immunotherapy unsafe or contraindicated (Turnstile II)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response assessed by immune-related response criteria and evaluated by positron emission tomography or computed tomography imaging
Time Frame:Up to 1 year
Safety Issue:
Description:Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline.

Secondary Outcome Measures

Measure:Number of CXCR2 transduced cells
Time Frame:At infusion
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.
Measure:Number of nerve growth factor receptor (NGFR) transduced (control) cells
Time Frame:At infusion
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.
Measure:Number of CXCR2 transduced cells based on tumor biopsy
Time Frame:Day 21
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.
Measure:Number of NGFR transduced cells based on tumor biopsy
Time Frame:Day 21
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.
Measure:Amount of CXCR2 cytokine
Time Frame:8 weeks
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.
Measure:Amount of CXCL8 cytokine
Time Frame:8 weeks
Safety Issue:
Description:Regression analysis will be used to estimate the ability of the genetically transduced T-cells to differentially recognize the cancer cell cytokines. Logistic regression will be used to assess the effects of immunological variables on the probability of clinical response.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

July 16, 2019