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Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4

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ClinicalTrials.gov Identifier: NCT02027935
Recruitment Status : Active, not recruiting
First Posted : January 6, 2014
Last Update Posted : June 21, 2018
Sponsor:
Collaborators:
Cancer Prevention Research Institute of Texas
American Association for Cancer Research
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 CD8+T cells with ipilimumab, cyclophosphamide, and IL-2 (aldesleukin). Researchers also want to learn if this combination can help to control metastatic melanoma (melanoma that has spread).

This study is divided into 2 parts: leukapheresis and treatment. In the leukapheresis part, blood cells will be collected from you to be made into modified CD8+T cells and given back to you in the treatment part.

CD8+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory, and they are designed to find melanoma cancer cells and may kill them.

Ipilimumab and aldesleukin are designed to increase the immune system's ability to fight cancer.

Cyclophosphamide will be used at a very low dose to weaken the body's natural defense against the T-cell transplant, so that the transplanted T-cells have a chance to grow and multiply.

This is an investigational study. CD8+T cells are not FDA approved or commercially available. They are currently being used for research purposes only. Cyclophosphamide, ipilimumab, and aldesleukin are FDA approved and commercially available for the way they are being used in this study.

Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Melanoma Drug: Cyclophosphamide Procedure: CD8+ T Cells Drug: Interleukin-2 Drug: Ipilimumab Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 for Patients With Metastatic Melanoma
Actual Study Start Date : January 22, 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: CD8+ T Cells + Cyclophosphamide + Interleukin-2 + Ipilimumab
Leukapheresis procedure performed to collect blood cells so they can be separated and grown as CD8+T cells. Cyclophosphamide administered at 300 mg/m2 by vein 2 days prior to T cell infusion. T cells administered at a dose of 10^10 cells/m2 by vein on Day 0. IL-2 250,000 U/m2 administered subcutaneously every 12 hours begins within 6 hours of T cell infusion and continues for a total of 14 days On Day 0 to Day +14. Ipilimumab administered 24 hours after T cell infusion at a dose of 3 mg/kg by vein. Subsequent infusions administered on Days +22, +43 and +64.
Drug: Cyclophosphamide
300 mg/m2 by vein 2 days prior to T cell infusion.
Other Names:
  • Cytoxan
  • Neosar

Procedure: CD8+ T Cells
T cells administered at a dose of 10^10 cells/m2 by vein on Day 0.

Drug: Interleukin-2
250,000 U/m2 administered subcutaneously every 12 hours begins within 6 hours of T cell infusion and continues for a total of 14 days On Day 0 to Day +14.
Other Names:
  • Aldesleukin
  • IL-2
  • Proleukin

Drug: Ipilimumab
3 mg/kg by vein 24 hours after T cell infusion. Subsequent infusions administered on Days +22, +43 and +64.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010




Primary Outcome Measures :
  1. Overall Response [ Time Frame: 12 weeks ]
    Radiographic imaging and clinical assessment of residual disease compared with pre-infusion assessment. A complete response (CR) defined as total regression of all tumor, 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). Assessment performed 12 weeks following T cell infusion and then every 3 months until disease progression or intervening therapy, and the overall response rate (OR) after 1 cycle (12) weeks.



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

Inclusion Criteria:

  1. Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease.
  2. Male or female subjects >/= 18 years of age.
  3. Expression of HLA-A2.
  4. ECOG/ Zubrod performance status of '0-1' at screening visit.
  5. 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.
  6. 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.
  7. Willing and able to give informed consent.
  8. Adequate venous access - consider PICC or central line.
  9. Evaluation of BRAFV600 mutation status.
  10. Measurable tumor (by RECIST criteria).
  11. MART 1 or SLC45A2 (+) staining results. (If patients have not had staining test in the past, the test will be run after patient consent is obtained, but before enrollment).

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening MRI or contrast CT). a) No signs or symptoms of CNS mets within the last 30 days (from enrollment evaluation). b) No single lesion larger than 1cm c) No more than 5 lesions
  4. 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.
  5. 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.
  6. Positive screening tests for HIV, Hep B, and Hep C (referencing blood draw at leukapheresis screening). If positive results are not indicative of true active or chronic infection, the patient can be treated.
  7. CBC and Chemistry profile prior to cyclophosphamide and T cell infusions: a) WBC </= 1000/uL b) Hct </= 24% or Hemoglobin </=8 g/dL c) ANC </= 500 d) Platelets </= 50,000 e) Creatinine >/= 3.0 x ULN f) AST/ALT >/= 2.5 x ULN, g) Bilirubin >/= 3 x ULN
  8. Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
  9. Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
  10. Patients may not be on any other treatments for their cancer aside from those included in the protocol. Patients may not undergo another form of treatment concurrently with this study.
  11. 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.

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): NCT02027935


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Cancer Prevention Research Institute of Texas
American Association for Cancer Research
Investigators
Principal Investigator: Adi Diab, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02027935     History of Changes
Other Study ID Numbers: 2012-1055
R1301 ( Other Identifier: Cancer Prevention Institute of Texas (CPRIT) )
SU2C-AACR-OT 1012 ( Other Identifier: American Association for Cancer Research )
NCI-2014-01040 ( Registry Identifier: NCI CTRP )
First Posted: January 6, 2014    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
Metastatic
CD8+ T cells
White blood cell
Leukapheresis
Cyclophosphamide
Cytoxan
Neosar
Interleukin-2
Aldesleukin
IL-2
Proleukin
Ipilimumab
Yervoy
BMS-734016
MDX010

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Aldesleukin
Interleukin-2
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents