Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01955460
Recruitment Status : Recruiting
First Posted : October 7, 2013
Last Update Posted : December 11, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This pilot phase I trial studies the side effects and best dose of genetically modified T-cells followed by aldesleukin in treating patients with stage III-IV melanoma. T-cells are a type of white blood cell that help the body fight infections. Genes that may help the T-cells recognize melanoma cells are placed into the T-cells in the laboratory. Adding these genes to the T cells may help them kill more tumor cells when they are put back in the body. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Biological: Aldesleukin Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Biological: NGFR-transduced Autologous T Lymphocytes Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the feasibility and safety of autologous transforming growth factor beta (TGFb) resistant (DNRII transduced) and NGFR transduced tumor infiltrating lymphocytes (TIL) in patients with metastatic melanoma.

SECONDARY OBJECTIVES:

I. To determine the survival and immune function of TGFb resistant (DNRII transduced) TIL in vivo.

II. To assess the anti-tumor effects of TGFb resistant (DNRII transduced) TIL.

OUTLINE: This is a dose-escalation study of TGFb DNRII-transduced autologous TIL and nerve growth factor receptor (NGFR)-transduced autologous T lymphocytes.

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 TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes 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 6 and 12 weeks, every 3 months for 1 year and then yearly for 10 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of 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
Actual Study Start Date : October 15, 2014
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, autologous T-cell immunotherapy)
Patients 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 TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes 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).
Biological: Aldesleukin
Given IV
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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- 138719

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: NGFR-transduced Autologous T Lymphocytes
Given IV

Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
Given IV
Other Name: TGFbDNRII-transduced Autologous TILs




Primary Outcome Measures :
  1. Generation of TGF alpha (TGFa)-DNRII and NGFR transduced tumor infiltrating lymphocytes (TILs) [ Time Frame: Up to 5 years ]
    Feasibility of generating TGFa-DNRII and NGFR transduced TILs and safety of treating patients with genetically modified T cells will be assessed. Feasibility will be defined as the production of virally transduced T cells and treatment of patients with these cells.


Secondary Outcome Measures :
  1. Response [ Time Frame: Up to 24 months ]
    Will be defined following immune-related response criteria as a 50% or greater decrease in the tumor's linear dimension post treatment compared to baseline.

  2. Number of DNRII transduced cells [ Time Frame: 6 months ]
    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a generalized linear mixed model (GLMM) approach may be used to model the DNRII/NGFR ratio over time.

  3. Number of NGFR transduced cells at infusion [ Time Frame: Day 0 ]
    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a GLMM approach may be used to model the DNRII/NGFR ratio over time.

  4. Number of NGFR transduced cells based on tumor biopsy [ Time Frame: Up to 24 months ]
    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a GLMM approach may be used to model the DNRII/NGFR ratio over time.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (treatment naive) will be eligible (Turnstile I)
  • Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability (Turnstile I)
  • 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)
  • Patients must have adequate TIL available (Turnstile II); pre-rapid expansion procedure (Pre-REP) TIL generated in the similar clinical trial 2004-0069 may also be utilized for Turnstile II
  • Patients must have at least one biopsiable measurable metastatic melanoma, lesion > or = to 1 cm (Turnstile II)
  • Patients may have brain lesions =< 1 cm each; the PI or designee will approve the treatment (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)
  • Patients with negative pregnancy test (urine or serum) must be documented within 14 days of screening for 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 menses at any time in the preceding 12 consecutive months) (Turnstile II)
  • Clinical performance status of ECOG 0-2 within 30 days of signing informed consent (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 aminotransferase (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 multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II)
  • Pulmonary function tests (forced expiratory volume in one second [FEV1] > 65% 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 (Turnstile II)

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)
  • Primary immunodeficiency and need for chronic steroid therapy, however prednisone is allowed at < 10 mg/day (Turnstile I)
  • Patients who are pregnant or nursing (Turnstile I)
  • Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent (Turnstile I)
  • Has had prior systemic cancer therapy within the past four weeks or v-raf murine sarcoma viral oncogene homolog B (B-RAF) or mitogen-activated protein kinase (MEK) inhibitors within 7 days at the time of the start of the lymphodepletion regimen (Turnstile II)
  • Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus (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)
  • 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; 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)

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): NCT01955460


Contacts
Layout table for location contacts
Contact: Rodabe N. Amaria, MD 713-792-2921

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Rodabe N. Amaria    713-792-2921      
Principal Investigator: Rodabe N. Amaria         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Rodabe N Amaria M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01955460    
Other Study ID Numbers: 2012-0758
NCI-2014-01211 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RP110553-P4
RM1012-012-1
2012-0758 ( Other Identifier: M D Anderson Cancer Center )
First Posted: October 7, 2013    Key Record Dates
Last Update Posted: December 11, 2020
Last Verified: December 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Aldesleukin
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents