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Adoptive Therapy Using Antigen-Specific CD4 T-Cells

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. Read our disclaimer for details. Identifier: NCT02210104
Recruitment Status : Withdrawn (Issues with tetramer staining)
First Posted : August 6, 2014
Last Update Posted : July 21, 2017
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn about the safety of giving CD4+T cells with ipilimumab and cyclophosphamide.

CD4+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory, and they are designed to find cancer cells and may kill them.

Condition or disease Intervention/treatment Phase
Melanoma Sarcoma Drug: Ipilimumab Drug: Cyclophosphamide Biological: CD4+ T cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Cellular Adoptive Immunotherapy Using Autologous CD4+ NY-ESO-1-Specific T Cells and Anti-CTLA4 For Patients With NY-ESO-1-Expressing Tumors
Study Start Date : December 2016
Estimated Primary Completion Date : December 2019

Arm Intervention/treatment
Experimental: Ipilimumab + Cyclophosphamide + CD4+T Cells
Starting Dose of Ipilimumab 1.0 mg /kg by vein on Days 1, 22, 43, and 64. Cyclophosphamide 300 mg/m2 administered intravenously 2 days prior to T cell infusion as an outpatient procedure. Antigen-specific CD4+ T cells administered at a dose 10^10 cells/m^2.
Drug: Ipilimumab
Starting Dose of Ipilimumab: 1.0 mg /kg by vein on Days 1, 22, 43, and 64.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Drug: Cyclophosphamide
300 mg/m2 administered intravenously 2 days prior to T cell infusion.
Other Names:
  • Cytoxan
  • Neosar

Biological: CD4+ T cells
Antigen-specific CD4+ T cells administered at a dose of 10^10 cells/m^2 on Day 0.

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Adoptively Transferred CD4 T Cells [ Time Frame: 12 weeks after T cell infusion ]
    (MTD) defined as dose level below that at which excessive toxicity was observed. Dose limiting toxicity: Any ≥ Grade 2 eye pain or reduction of visual acuity that does not respond to topical therapy and does not improve to ≤ Grade 1 severity within 2 weeks of starting therapy requires systemic treatment; Any ≥ Grade 3 bronchospasm or other hypersensitivity reaction; Any adverse event, laboratory abnormality or intercurrent illness which, in the judgment of the Investigator, presents a substantial clinical risk to the patient with continued dosing; Any other ≥ Grade 3 non-skin related adverse event.

Secondary Outcome Measures :
  1. Clinical Response [ Time Frame: 6 weeks after T cell infusion ]
    Complete response (CR) defined as total regression of all tumors, a partial response (PR) as 30% or greater decrease in the sum of the longest diameter of target lesions and progressive disease (PD) as 20% increase in the sum of the longest diameter of target lesions (modified world health organization criteria or mWHO. Radiographic imaging (as clinically indicated) and clinical assessment of residual disease compared with pre-infusion assessment.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histopathologic documentation of melanoma, synovial sarcoma or mixed round cell liposarcoma concurrent with the diagnosis of metastatic disease.
  2. Tumor expression of NY-ESO-1 (2+ staining or > 25%) by IHC.
  3. Male or female subjects ≥18 years of age.
  4. Expression of HLA-DPB1*0401
  5. Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of '0-1' .
  6. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
  7. Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP.
  8. Willing and able to give informed consent.
  9. Adequate venous access - consider peripherally inserted central venous catheter (PICC) or central line
  10. Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray or CT scan)
  11. At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy, radiotherapy, or major surgery.
  12. At least 6 weeks must have elapsed since the last nitrosoureas, mitomycin C and liposomal doxorubicin
  13. Toxicity related to prior therapy must either have returned to < or equal to grade 1, baseline, or been deemed irreversible

Exclusion Criteria:

  1. Patients with active infections or oral temperature > 38.2 C within 71 hours of Leukapheresis. The procedure may be deferred.
  2. Patients with Hct <30%, white blood count (WBC) <2500/uL and platelets <50,000 immediately prior to Leukapheresis. The procedure may be deferred.
  3. Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix.
  4. Complete blood count (CBC) and Chemistry profile prior to cyclophosphamide and T cell infusions: WBC < 2000/uL Hct < 24% or Hb < 8 g/dL absolute neutrophil count (ANC) < 1000 Platelets < 50,000 Creatinine > 3.0 x ULN AST/ALT > 2.5 x ULN Bilirubin > 3 x ULN
  5. Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
  6. Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded.
  7. Significant cardiovascular abnormalities as defined by any one of the following: Congestive heart failure, Clinically significant hypotension, Symptoms of coronary artery disease, Presence of cardiac arrhythmias on EKG requiring drug therapy,Ejection fraction < 50 % (echocardiogram or MUGA).
  8. Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening MRI or contrast CT).
  9. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
  10. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
  11. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not indicative of true active or chronic infection, the patient can be treated.
  12. Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
  13. Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
  14. No prisoners or children will be enrolled on this study

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 identifier (NCT number): NCT02210104

Sponsors and Collaborators
M.D. Anderson Cancer Center
National Institutes of Health (NIH)
National Cancer Institute (NCI)
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Principal Investigator: Cassian Yee, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02210104    
Other Study ID Numbers: 2013-0669
R01CA104711-09 ( U.S. NIH Grant/Contract )
First Posted: August 6, 2014    Key Record Dates
Last Update Posted: July 21, 2017
Last Verified: July 2017
Keywords provided by M.D. Anderson Cancer Center:
Mixed round cell liposarcoma
CD4+T Cells
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological