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Trial record 2 of 535 for:    Study of MK-3475

Study of MK-3475 in Conjunction With Lymphodepletion, TIL, and High or Low Dose Interleukin-2 (IL-2) in Patients With Metastatic Melanoma

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Prometheus Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02500576
First received: July 14, 2015
Last updated: June 15, 2017
Last verified: June 2017
  Purpose

The goal of this clinical research study is to learn if pembrolizumab, an infusion of T-cells, chemotherapy (cyclophosphamide and fludarabine), and either high or low dose interleukin-2 (IL-2) can help to control metastatic melanoma. The safety of this drug combination will also be studied.

T-cells are white blood cells in your body that are important to the immune system. The T-cells used in this study will be collected and grown in a separate study (MD Anderson Protocol 2004-0069).


Condition Intervention Phase
Melanoma Drug: Cyclophosphamide Drug: Mesna Drug: Fludarabine Procedure: TIL (T-cells) Drug: IL-2 Drug: MK-347 Behavioral: Questionnaires Behavioral: Phone Calls Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Study of MK-3475 in Conjunction With Lymphodepletion, TIL, and High or Low Dose Interleukin-2 (IL-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:
  • Overall Response Rate (ORR) [ Time Frame: 21 days ]
    ORR computed separately by arm and presented with exact 95% confidence intervals. ORR compared between the two treatment arms by using Fisher's exact test. Association between ORR and the same covariates assessed by using logistic regression. ORR endpoint monitored using a Bayesian sequential monitoring rule (Thall et all, 1995).


Estimated Enrollment: 36
Actual Study Start Date: August 7, 2015
Estimated Study Completion Date: August 1, 2020
Estimated Primary Completion Date: August 1, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose IL-2 + Lymphodepleting Chemotherapy + TIL Infusion

Participants receive high dose IL-2 after standard lymphodepleting chemotherapy and TIL infusion.

Cyclophosphamide administered at 60 mg/kg/day by vein on Days -7 and -6. Mesna 60 mg/kg by vein on Days -7 and -6. Fludarabine 25 mg/m2 by vein on Days -5 to -1. On day 0, TIL infused as an inpatient by vein approximately 15-60 minutes depending on the volume of cells infused. Up to 150 billion cells infused.

Participants receive high dose IL-2 at dose of 720,000 IU/kg by vein every 8-16 hours for up to 15 doses starting 12-16 hours after T cell infusion on Day 1.

If participants develop stable or partially responding disease, up to 31 doses (2 years) of MK-3475, 200 mg by vein every 21 days.

Questionnaires completed about quality of life at baseline, Day 63, then every 12 weeks.

After 2 years of pembrolizumab, phone calls made by study staff to participant every 3 months.

Drug: Cyclophosphamide
60 mg/kg/day by vein on Days -7 and -6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Mesna
60 mg/kg by vein on Days -7 and -6.
Other Name: Mesnex
Drug: Fludarabine
25 mg/m2 by vein on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Procedure: TIL (T-cells)
On day 0, TIL infused as an inpatient by vein approximately 15-60 minutes depending on the volume of cells infused. Up to 150 billion cells infused.
Drug: IL-2

High dose IL-2 Group: 720,000 IU/kg by vein every 8-16 hours for up to 15 doses starting 12-16 hours after T cell infusion on Day 1.

Low Dose IL-2 Group: 2 million IU/kg subcutaneously for 14 days starting 12-16 hours after T cell infusion on Day 1.

Other Names:
  • Aldesleukin
  • Interleukin-2
  • Proleukin
Drug: MK-347
If participants develop stable or partially responding disease, up to 31 doses (2 years) of MK-3475, 200 mg by vein every 21 days.
Other Names:
  • Keytruda
  • Pembrolizumab
  • SCH-900475
Behavioral: Questionnaires
Questionnaires completed at baseline, Day 63, then every 12 weeks.
Other Name: Surveys
Behavioral: Phone Calls
After 2 years of pembrolizumab, phone calls made by study staff to participant every 3 months.
Experimental: Low Dose IL-2 + Lymphodepleting Chemotherapy + TIL Infusion

Participants receive low dose IL-2 after standard lymphodepleting chemotherapy and TIL infusion.

Cyclophosphamide administered at 60 mg/kg/day by vein on Days -7 and -6. Mesna 60 mg/kg by vein on Days -7 and -6. Fludarabine at 25 mg/m2 by vein on Days -5 to -1. On day 0, TIL infused as an inpatient by vein approximately 15-60 minutes depending on the volume of cells to be infused. Up to 150 billion cells infused.

Participants receive low dose IL-2 at 2 million IU/kg subcutaneously for 14 days starting 12-16 hours after T cell infusion on Day 1.

If participants develop stable or partially responding disease, up to 31 doses (2 years) of MK-3475, 200 mg by vein every 21 days.

Questionnaires completed about quality of life at baseline, Day 63, then every 12 weeks.

After 2 years of pembrolizumab, phone calls made by study staff to participant every 3 months.

Drug: Cyclophosphamide
60 mg/kg/day by vein on Days -7 and -6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Mesna
60 mg/kg by vein on Days -7 and -6.
Other Name: Mesnex
Drug: Fludarabine
25 mg/m2 by vein on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Procedure: TIL (T-cells)
On day 0, TIL infused as an inpatient by vein approximately 15-60 minutes depending on the volume of cells infused. Up to 150 billion cells infused.
Drug: IL-2

High dose IL-2 Group: 720,000 IU/kg by vein every 8-16 hours for up to 15 doses starting 12-16 hours after T cell infusion on Day 1.

Low Dose IL-2 Group: 2 million IU/kg subcutaneously for 14 days starting 12-16 hours after T cell infusion on Day 1.

Other Names:
  • Aldesleukin
  • Interleukin-2
  • Proleukin
Drug: MK-347
If participants develop stable or partially responding disease, up to 31 doses (2 years) of MK-3475, 200 mg by vein every 21 days.
Other Names:
  • Keytruda
  • Pembrolizumab
  • SCH-900475
Behavioral: Questionnaires
Questionnaires completed at baseline, Day 63, then every 12 weeks.
Other Name: Surveys
Behavioral: Phone Calls
After 2 years of pembrolizumab, phone calls made by study staff to participant every 3 months.

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Turnstile I - Screening: Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease.
  2. Patients must have a lesion amenable to resection for the generation of TIL on MD Anderson Protocol 2004-0069.
  3. Patients must receive an MRI/CT/PET of the brain within 6 months of signing informed consent. If new CNS lesions are present, patient must have definitive treatment (including surgery or radiation). PI or his designee should make final determination regarding enrollment.
  4. Age greater than or equal to 18 years.
  5. Clinical performance status of ECOG 0 - 1 within 30 days of signing informed consent.
  6. Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naïve) will be eligible.
  7. Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability.
  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).
  9. Turnstile II - Treatment: Patients must sign the treatment consent document before Turnstile II screening procedures. Before the treatment starts and at each visit, the patient will be asked to complete two quality of life questionnaires. It should take about 15 minutes to complete the questionnaires (FACT-G, FACT-Melanoma). Patients must fulfill all of the following criteria to be eligible for Turnstile II of the study.
  10. Patients must have adequate TIL that were previously harvested and then cryopreserved on MDACC protocol 2004-0069.
  11. Patients who have had prior therapy (BRAF inhibitors, ipilimumab, anti PD-1 antibody or anti PD-L1 antibody) or treatment naïve patients are eligible as long as toxicity from therapy is grade </= 1 or at baseline.
  12. Patients must have at least one biopsiable measurable metastatic melanoma, lesion > 1cm and must be amenable to undergoing serial biopsies through the course of therapy. This lesion must not be documented as one of the target lesions
  13. Patients may have CNS metastases which have been treated and are radiographically stable for at least 4 weeks
  14. 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 menstruated in the past 12 months and without sterilization surgery.
  15. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), or if the patient is post-menopausal, 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.
  16. Pregnancy testing will be performed 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).
  17. Clinical performance status of ECOG 0-1 within 30 days of signing consent
  18. A stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 1 month of lymphodepletion.
  19. 12-lead EKG showing no active ischemia and QTc interval less than 480 msec
  20. Pulmonary function tests (FEV1>65% or FVC>65% of predicted) within 1 month of lymphodepletion.
  21. Have measurable disease based on RECIST 1.1 and irRC criteria
  22. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.
  23. System Hematological Absolute neutrophil count (ANC) >/= 1,500 /mcL; Platelets >/= 100,000 / mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L Renal Serum creatinine OR Measured or calculated a creatinine clearance (GFR can also be used in place of creatinine or CrCl) </= 1.5 X upper limit of normal (ULN) OR >/= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic Serum total bilirubin </= 1.5 X ULN OR Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) </= 2.5 X ULN OR </= 5 X ULN for subjects with liver metastases.
  24. Contd #23: Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

Exclusion Criteria:

  1. Turnstile I - Screening: 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
  2. Primary immunodeficiency and need for chronic steroid therapy, Exception: Patients on chronic physiologic dose of steroid equivalent to prednisone < 10 mg/day is allowed.
  3. Patients who are pregnant or nursing.
  4. Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent.
  5. Turnstile II - Treatment: Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
  6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiation of lymphodepletion. Exception: Patients on chronic physiologic dose of steroid equivalent to prednisone < 10 mg/day is allowed.
  7. Has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to investigational or standard agents administered more than 4 weeks earlier.
  8. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to lymphodepletion or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with </= Grade 2 neuropathy, alopecia, hypophysitis stable on physiologic dose of steroid equivalent to prednisone < 10 mg/day, hypothyroidism stable on hormone replacement are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to initiation of lymphodepletion.
  11. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. Subjects with hypophysitis stable on physiologic dose of steroid will not be excluded from the study.
  12. Has evidence of interstitial lung disease or has a history of non-infectious pneumonitis that required steroids or current pneumonitis.
  13. Has an active infection requiring systemic therapy.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  19. 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.
  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: NCT02500576

Contacts
Contact: Rodabe N. Amaria, MD 713-792-2921

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Prometheus Inc.
Investigators
Principal Investigator: Rodabe N. Amaria, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02500576     History of Changes
Other Study ID Numbers: 2014-0922
NCI-2015-01395 ( Registry Identifier: NCI CTRP )
Study First Received: July 14, 2015
Last Updated: June 15, 2017

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:
MK-3475
Keytruda
Pembrolizumab
Melanoma
Metastatic
Cyclophosphamide
Cytoxan
Neosar
Mesna
Mesnex
Fludarabine
Fludarabine phosphate
SCH-900475
IL-2
Aldesleukin
Interleukin-2
Proleukin
TIL
T-cells
Questionnaires
Surveys
Phone calls

Additional relevant MeSH terms:
Pembrolizumab
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Mesna
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
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on July 21, 2017