Ipilimumab With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Melanoma Mets Pts

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01701674
First received: October 3, 2012
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The investigators want to study the safety, side effects, and benefits of TILs when they are given with the drug ipilimumab. Ipilimumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other diseases.


Condition Intervention
Metastatic Melanoma
Drug: Ipilimumab
Procedure: Tumor Infiltrating Lymphocytes (TIL)
Drug: Administration of Lymphodepletion
Drug: Cyclophosphamide as Part of Lymphodepletion
Drug: Fludarabine as Part of Lymphodepletion
Drug: High Dose IL-2
Biological: Adoptive Cell Therapy with TIL

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Co-stimulation With Ipilimumab to Enhance Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Safety and Feasibility of Administering Ipilimumab with adoptive cell transfer (ACT) Using TIL [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The data analysis will mainly be descriptive. All study results will be preliminary and of exploratory in nature due to the pilot status and small sample size of the trial. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥6/10) of the patients with TIL. All patients will be evaluable for toxicity from the time of their first protocol treatment. Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.


Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Overall response (OR) is defined as the patient being alive at week 6, confirmed at week 12 and tumor size evaluated at both times using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria to be a complete response (CR) or partial response (PR). Evaluations will be made by computed tomography (CT) scan approximately 6 weeks after the cell infusion, then confirmed by CT scanning approximately 12 weeks after the cell infusion, and by clinical evaluation during the first 12 weeks. The overall response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution.

  • Progression Free Survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Confidence intervals for the median and survival rates at different time points will be constructed if needed and appropriate. This secondary endpoint will be reported descriptively.


Estimated Enrollment: 10
Study Start Date: October 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Therapy
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Drug: Ipilimumab
Pre-treatment with ipilimumab (cycle 1): Before the participant's tumor sample is taken to send to the lab for growing the TILs, they will start their first cycle of ipilimumab. This drug is given as an intravenous infusion (through a vein) over a period of about 90 minutes (an hour and a half). Cycle 2 of ipilimumab: About a week after the sample of the participant's tumor was collected for TIL growth (and 3 weeks after their first cycle of ipilimumab), participant's will have their second cycle of ipilimumab. This will be another IV infusion, lasting about 90 minutes.
Other Name: Yervoy
Procedure: Tumor Infiltrating Lymphocytes (TIL)
Tumor sample for TIL growth in the lab: About 2 weeks after the participant's first cycle of ipilimumab, a sample of their tumor will be collected and sent to the lab for TIL growth. Growing the TILs takes about 6 weeks. If their sample has grown enough TIL cells, participants will continue with the next part of the study. Depending on how long the TILs take to grow in the lab, they may need to repeat some of their laboratory and imaging tests (blood draws, X-rays, and CT or magnetic resonance imaging [MRI] scans). TIL Infusion (inpatient): After completing lymphodepletion, participants will be admitted back into the hospital for IV infusion of the TIL cells.
Drug: Administration of Lymphodepletion
Lymphodepletion (inpatient hospital stay for about 2 days plus outpatient drug dosing for 5 days): About 4 weeks after their second cycle of ipilimumab, participants will be admitted to the hospital for their first two days of receiving the chemotherapy drug, cyclophosphamide. This drug will be given as an intravenous (IV, meaning through the vein) infusion. After 2 days of receiving cyclophosphamide, if their study doctor thinks that they are well enough, you will be discharged from the hospital and will return for the next 5 days in a row for outpatient IV infusions of the second lymphodepletion chemotherapy, fludarabine.
Drug: Cyclophosphamide as Part of Lymphodepletion
Other Name: Cytoxan
Drug: Fludarabine as Part of Lymphodepletion
Other Name: Fludara
Drug: High Dose IL-2
High dose IL-2 (continued inpatient): Participants will remain in the hospital following TIL infusion for receiving high dose IL-2 and recovery. The IL-2 will be given three times per day for about 3-5 days as an IV bolus (meaning through the vein, more quickly than other infusions - in about 15 minutes each dose). Participants will remain in the hospital for approximately 7-14 days until they have recovered from the IL-2 treatments.
Other Names:
  • Interleukin-2
  • Aldesleukin
  • Proleukin
Biological: Adoptive Cell Therapy with TIL
Other Name: ACT

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have unresectable metastatic stage IV melanoma or stage III intransit or regional nodal disease, and in the opinion of the institutional PI is an acceptable candidate for ACT with high dose IL-2
  • Residual measurable disease after resection of target lesion(s) for TIL growth
  • Tumor may have a B-RAF V600 mutation or be BRAF wild type, and patients must not have been previously treated with ipilimumab
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1. ECOG performance status of 0-1 will be inferred if the patient's level of energy is ≥ 50% of baseline.
  • May have been previously treated for metastatic disease, or may have not had prior systemic treatment. Patients with a V600 BRAF mutated tumor may have previously received a prior BRAF inhibitor.
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of screening.
  • Adequate renal, hepatic and hematologic function, including creatinine of less than or equal to 1.7 gm/dL, 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, aspartate aminotransferase (AST) and alanine transaminase (ALT) of less than 3 X institutional upper limit of normal, hemoglobin of 8 gm/dL or more, white blood count (WBC) of 3000 per mcL and total granulocytes of 1000 per mcL or more, and platelets of 100,000 per mcL or more.
  • Must have a positive screening Epstein-Barr virus (EBV) antibody titre on screening test
  • Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.
  • At screening, patients with ≤ 3 untreated CNS metastases may be included provided none of the untreated lesions are > 1 cm in greatest dimension, and there is no peri-tumoral edema present on brain imaging (MRI or CT if MRI is contraindicated).
  • At screening, patients with central nervous system (CNS) metastases treated with either surgical resection and/or radiation therapy may be included. Patients may be included if the largest lesion is ≤ 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment.
  • At screening, patients may be included if the largest lesion is > 1 cm or > 3 in number, and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
  • No evidence of ongoing cardiac dysrhythmia ≥ grade 2 (NCI Common Terminology Criteria for Adverse Events [CTCAE], v4.0)
  • All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document, with the exceptions of: negative serum pregnancy test for women of child-bearing potential which must be negative within 7 days of screening, human leukocyte antigen (HLA) typing which will not be repeated if performed previously, and pulmonary function tests (PFTs)/cardiac stress tests whose results are valid for 6 months if performed previously.

Exclusion Criteria:

  • Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the principal investigator (PI) or treating coinvestigator is not acceptable risk for ACT, are excluded.
  • Patients testing positive for HIV titre, Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, Human T-Lymphotropic Virus (HTLV) I or II antibody, or both Rapid. Plasma Reagin (RPR) and fluorescent treponemal antibodies (FTA) positive are excluded.
  • Pregnant or nursing
  • Patients needing chronic, immunosuppressive systemic steroids are excluded
  • History of autoimmune disease that require immunosuppressive medications at the time of screening
  • 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
  • Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema
  • Patients with ≤ 3 untreated CNS metastases but with at least one lesion >1 cm or peri-tumoral edema
  • Patients with invasive malignancy other than melanoma at the time of enrollment and within 2 years prior to the first TIL administration are excluded, except for adequately treated (with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years.
  • Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
  • Unable to comprehend and give informed consent
  • Male patients with WOCBP partners who do not agree to use two FDA-accepted forms of contraception during sexual intercourse with women of child-bearing potential from the start of ipilimumab and up to at least 6 months after ACT
  • WOCBP who do not agree to use 2 FDA forms of contraception during sexual intercourse from the start of ipilimumab and up to at least 6 months after ACT
  • Patients who have received ipilimumab in the past
  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: NCT01701674

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Erica Royster    813-745-4279    erica.royster@moffitt.org   
Principal Investigator: Amod Sarnaik, M.D.         
Sub-Investigator: Heather Bridge, PA-C         
Sub-Investigator: Ronald DeConti, M.D.         
Sub-Investigator: Geoffrey Gibney, M.D.         
Sub-Investigator: William Janssen, Ph.D.         
Sub-Investigator: Ragini Kudchadkar, M.D.         
Sub-Investigator: Vernon Sondak, M.D.         
Sub-Investigator: Melissa Thebeau, ARNP         
Sub-Investigator: Jeffrey Weber, M.D., Ph.D.         
Sub-Investigator: Jonathan Zager, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Amod Sarnaik, M.D. H. Lee Moffit Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01701674     History of Changes
Other Study ID Numbers: MCC-17057, CA184-213
Study First Received: October 3, 2012
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
skin cancer

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
Fludarabine monophosphate
Fludarabine
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
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
Peripheral Nervous System Agents
Central Nervous System Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 28, 2014