Prospective Randomized Comparative Study of Cell Transfer Therapy Using CD8+-Enriched Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-Dose Aldesleukin in M...

NCT01118091 | Completed Phase 2 Results

• 2 other identifiers: 10011710-C-0117
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Adoptive cell therapy involves taking white blood cells called lymphocytes from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient to allow the cells to attack the tumor. Because this process is lengthy and difficult to perform, researchers have been developing improved means of performing adoptive cell therapy. Researchers are now interested in comparing adoptive cell therapy with the standard treatment for metastatic melanoma (skin cancer). Objectives: \- To compare the effectiveness of adoptive cell therapy with standard high-dose aldesleukin as a treatment for metastatic melanoma. Eligibility:

• Individuals 18 years of age or older who have been diagnosed with metastatic melanoma and have not previously received aldesleukin therapy or cell therapy for their disease.
• Participants must have at least one tumor that can be easily removed as part of the treatment procedure. Design:
• Participants will be screened with a full medical history, physical examination, blood and urine tests, and imaging scans to evaluate tumor size and treatment options.
• Participants will be separated into two groups, in which one group will have adoptive cell therapy and one will have aldesleukin treatment.
• Adoptive Cell Therapy
• Participants will have a tumor sample taken in order to collect white blood cells for treatment. Participants whose tumors do not provide sufficient white blood cells may be switched to the aldesleukin-only treatment group.
• The white blood cells will be grown in the laboratory for several weeks.
• Prior to receiving cell therapy, participants will receive chemotherapy for 7 days to improve the chances of successful treatment.
• Participants will have cell therapy followed by high-dose aldesleukin treatment every 8 hours for up to 5 days. This treatment will be followed by 1 to 2 weeks of recovery time as an inpatient at the clinical center.
• Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter..
• Standard Aldesleukin Treatment
• Participants will have high-dose aldesleukin treatment every 8 hours for up to 5 days (one cycle of treatment), and will have a second cycle of treatment 7 to 10 days after the first cycle.
• If tests show that the tumors have grown, participants will be offered the chance to have additional cycles of aldesleukin, or begin a cell therapy treatment.
• Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter.

Conditions

Skin Cancer; Melanoma; Metastatic Melanoma

Keywords

Immunotherapy; Metastatic Melanoma; Randomized; Cell Therapy; Skin Cancer; Melanoma

Outcome Measures

Primary Outcomes (2)

• Response Rate

  Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.

  3 years

• Progression Free Survival

  Measured from the time of randomization to time of progression (or death).

  3 years

Secondary Outcomes (1)

• Toxicity

  3 years

Study Arms (2)

Arm 1-Aldesleukin

ACTIVE COMPARATOR

Aldesleukin 720,000 IU/kg IV over 15 minute every eight hours and continuing for up to 5 days (maximum of 15 doses). Patients will receive one additional cycle of aldesleukin approximately 10-14 days after completion of the first cycle of aldesleukin.

Biological: Aldesleukin

Arm 2 - Adoptive cell therapy

EXPERIMENTAL

Adoptive Cell Therapy consisting of the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of between 1x10\^9 to 2x10\^11 CD8+ enriched tumor infiltrating lymphocytes (minimum of 5 x10\^8) and the administration of high-dose aldesleukin.

Biological: CD8 enriched Young TIL

Interventions

Aldesleukin BIOLOGICAL

Aldesleukin 720,000 IU/kg IV over 15 minute every eight hours and continuing for up to 5 days (maximum of 15 doses). Patients will receive one additional cycle of aldesleukin approximately 10-14 days after completion of the first cycle of aldesleukin.

Arm 1-Aldesleukin

CD8 enriched Young TIL BIOLOGICAL

Adoptive Cell Therapy consisting of the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of between 1x10\^9 to 2x10\^11 CD8+ enriched tumor infiltrating lymphocytes (minimum of 5 x 10\^8) and the administration of high-dose aldesleukin.

Arm 2 - Adoptive cell therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation. The lesion must be of at least 2cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization is less than or equal to 7 days).
• Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
• No prior high-dose aldesleukin therapy at a dose of greater than or equal to 600,000 IU/kg.
• Greater than or equal to 18 years of age.
• Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
• Life expectancy of greater than three months.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Hematology:
• Absolute neutrophil count greater than 1000/mm\^3 without support of filgrastim
• Normal White blood cell (WBC) (\> 3000/mm\^3).
• Hemoglobin greater than 8.0 g/dl
• Platelet count greater than 100,000/mm\^3
• k. Serology:

You may not qualify if:

• Prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Systemic steroid therapy requirement.
• Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and Acquired Immunodeficiency Syndrome (AIDS)).
• Opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms.
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
• In patients \> 60 years old, documented LVEF of less than or equal to 45%.
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking
• Symptoms of respiratory dysfunction

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

  PMID: 17237035 BACKGROUND

• Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4.

  PMID: 10685652 BACKGROUND

• Kirkwood MW, Yeates KO, Taylor HG, Randolph C, McCrea M, Anderson VA. Management of pediatric mild traumatic brain injury: a neuropsychological review from injury through recovery. Clin Neuropsychol. 2008 Sep;22(5):769-800. doi: 10.1080/13854040701543700. Epub 2007 Sep 1.

  PMID: 17896204 BACKGROUND

MeSH Terms

Conditions

Skin Neoplasms; Melanoma

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas

Results Point of Contact

• Title: Dr. Steven Rosenberg
• Organization: National Cancer Institute, National Institutes of Health

sar@mail.nih.gov

301-496-4164

Study Officials

• Ramaprasad Srinivasan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 6, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 8, 2015
• Results First Posted: June 3, 2013

Record last verified: 2015-09

Locations

US (1)