Tumor Infiltrating Lymphocytes (TIL) Transduced With TGFbDNRII

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
CPRIT
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01955460
First received: September 27, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of T-cells injected with the genes TGFb-DNR and NGFR that can be given in combination with chemotherapy (cyclophosphamide and fludarabine) and aldesleukin to patients with metastatic melanoma.

This study involves gene therapy. T-cells are types of white blood cells that help your body fight infections. They may recognize and kill melanoma cells. Researchers want to grow your T-cells in a laboratory, inject them with TGFb-DNR and NGFR genes which may help them recognize tumor cells, and then give them back to you by vein. This may help to control melanoma.

Cyclophosphamide is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.

Aldesleukin is designed to block the activity of cells that decrease the immune system's ability to fight cancer.


Condition Intervention Phase
Melanoma
Drug: Cyclophosphamide
Drug: Mesna
Drug: Fludarabine monophosphate
Biological: T-Cells
Drug: Interleukin-2 (IL-2)
Behavioral: Questionnaires
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lymphodepletion Plus Adoptive Cell Transfer With TGF-Beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Maximum Tolerated Dose (MTD) defined as the dose having posterior mean probability to toxicity closest to the targeted value .20.


Estimated Enrollment: 36
Study Start Date: August 2014
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T-Cells + Chemotherapy
Patients receive T-cells transduced with DNRII as well as T- cells transduced with NGFR (as a control gene). Cytoxan administered at 60 mg/kg/day by vein over approximately 2 hours on Days -7 and -6. Mesna 60 mg/kg by vein over 24 hours on Days -7 and -6. Fludarabine 25 mg/m2 by vein daily over approximately 15-30 minutes on Days -5 to -1. On day 0, all patients receive assigned dose level of transduced DNRII TIL, with an equal number of transduced NGFR TIL, up to a total of 1.5 x 10^11 TIL in NS. Five dose levels of DNRII transduced TIL to be evaluated are 15 x 10^9, 30 x 10^9, 45 x 10^9, 60 x 10^9 and 75 x 10^9 DNRII transduced TIL. Twelve (12) to sixteen (16) hours after completing the T cell infusion, all patients receive high dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over an approximate 15 minute period every 8-16 hours for up to 15 doses on Days 1 to 5 and 22-26.
Drug: Cyclophosphamide
60 mg/kg/day by vein on Day -7 and -6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Mesna
60 mg/kg by vein on Day -7 and -6.
Other Name: Mesnex
Drug: Fludarabine monophosphate
25 mg/m2 by vein on Day -5 to Day -1.
Other Names:
  • Fludarabine phosphate
  • Fludara
Biological: T-Cells
Starting dose level of DNRII transduced TIL T-cells: 15 x 10^9 by vein on Day 0.
Drug: Interleukin-2 (IL-2)
720,000 IU/kg by vein every 8-16 hours for up to 15 doses on Days 1 to 5 and 22 to 26.
Other Names:
  • Aldesleukin
  • IL-2
  • Proleukin
Behavioral: Questionnaires
Quality of life (QOL) questionnaires completed at baseline, 6 and 12 weeks after T-cell infusion, at 6 month follow up, then yearly.
Other Name: Surveys

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease (turnstile I).
  2. Patients must have a lesion amenable to resection for the generation of TIL (Turnstile I).
  3. Patients must receive an MRI/CT/PET of the brain within 6 months of signing informed consent. If new lesions are present, patient must have definitive treatment. PI or his designee should make final determination regarding enrollment (Turnstile I).
  4. Age greater than or equal to 7 years (Turnstile I).
  5. Clinical performance status of ECOG 0-2 within 30 days of signing informed consent (Turnstile I).
  6. Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible (Turnstile I).
  7. Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability (Turnstile I).
  8. 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 (i.e. who has not had menses at any time in the preceding 12 consecutive months) (Turnstile I).
  9. Patients must have adequate TIL available (Turnstile II). Pre-REP TIL generated in the similar clinical trial 2004-0069 may also be utilized for Turnstile II.
  10. Patients must have at least one biopsiable measurable metastatic melanoma, lesion > or = to1cm (Turnstile II).
  11. Patients may have brain lesions, which measure < or = to 1cm each (Turnstile II).
  12. 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).
  13. 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, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control (Turnstile II).
  14. Pregnancy testing will be performed within 14 days prior to start of lymphodepletion (Turnstile II).
  15. Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (Turnstile II).
  16. Absolute neutrophil count greater than or equal to 1000/mm3 (Turnstile II).
  17. Platelet count greater than or equal to 100,000/mm3 (Turnstile II).
  18. Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II).
  19. Serum ALT less than three times the upper limit of normal (Turnstile II).
  20. Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II).
  21. 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).
  22. A stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II).
  23. Pulmonary function tests (FEV1>65% or FVC>65%of predicted) within 6 months of lymphodepletion (Turnstile II).
  24. MRI/CT/PET of the brain within 30 days of lymphodepletion (Turnstile II).

Exclusion Criteria:

  1. 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).
  2. Patients who are pregnant or nursing (Turnstile I).
  3. Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent (Turnstile I).
  4. Has had prior systemic cancer therapy within the past four weeks or B-RAF or MEK inhibitors within 7 days at the time of the start of the lymphodepletion regimen (Turnstile II).
  5. Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus (Turnstile II).
  6. 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).
  7. Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm3), WBC (> 3,000/mm3) or absence of opportunistic infections (Turnstile II).
  8. Require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks prior to lymphodepletion (Turnstile II).
  9. 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).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01955460

Contacts
Contact: Patrick Hwu, MD 713-792-2921

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
CPRIT
Investigators
Principal Investigator: Patrick Hwu, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01955460     History of Changes
Other Study ID Numbers: 2012-0758, RP110553-P4
Study First Received: September 27, 2013
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
Interleukin-2
Metastatic
T-cells
Autologous tumor infiltrating lymphocytes
TIL
DNRII
NGFR
Cyclophosphamide
Cytoxan
Neosar
Mesna
Mesnex
Fludarabine
Fludarabine phosphate
Fludara
IL-2
Aldesleukin
Proleukin
Questionnaires
Surveys
Quality of life
QOL

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Interleukin-2
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Mesna
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Vidarabine
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on July 24, 2014