Chemotherapy Followed by gp100 Lymphocytes and Aldesleukin to Treat Melanoma

NCT00665470 | Completed Phase 2 Results DMC

• 2 other identifiers: 08010408-C-0104
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: This study uses a new experimental procedure for treating melanoma that uses the patient's own lymphocytes (type of white blood cell), which are specially selected to target and destroy their tumor. Objectives: To determine whether this experimental treatment can cause the patient's tumor to shrink. To test the safety of the treatment and its effects on the immune system. Eligibility: Patients with metastatic melanoma 18 years of age and older for whom standard treatments are not effective or who cannot take high-dose interleukin-2 (IL-2). Patients must have the tissue type human leukocyte antigens (HLA-A)0201. Design: Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed. Patients have leukapheresis (a procedure for collecting lymphocytes that is similar to collecting whole blood) to collect cells for laboratory treatment and later reinfusion. Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the cultured lymphocytes. Cell infusion and IL-2 treatment: Patients receive the lymphocytes by infusion through a vein and then either high-dose IL-2 infused through a vein or low-dose IL-2 injected under the skin. High-dose IL-2 is given as infusions through a vein every 8 hours for up to 15 doses. Low-dose IL-2 is given as injections under the skin daily for 5 days, followed by a 2-day rest, with this regimen repeated for a total of 5 weeks. Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and IL-2. Tumor biopsy: Patients may be asked to have a biopsy (removal of a small piece of tumor) after receiving treatment to look at the effects of treatment in the tumor. Follow-up: After treatment is completed, patients return to the clinic for physical examinations, review of side effects, laboratory tests and scans every 1 to 6 months until the disease worsens. Retreatment: Patients whose tumor did not grow after treatment or showed evidence of shrinking may be able to be retreated if their tumor begins to grow. They receive the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment....

Conditions

Skin Cancer; Metastatic Melanoma

Keywords

Malignant Melanoma; HLA-A2; Immunotherapy; Clinical Response; Skin Cancer

Outcome Measures

Primary Outcomes (2)

• Response

  Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a 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. Progression (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more 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.

  30 months

• Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V3.0

  Here is the number of participants with adverse events. For a detailed list of participants with adverse events, see the adverse event module.

  16 months

Study Arms (2)

Cohort I - high dose Aldesleukin

EXPERIMENTAL

Patients receive high-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).

Drug: Aldesleukin

Cohort II - low dose Aldesleukin

EXPERIMENTAL

Beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion, patients receive low-dose aldesleukin subcutaneous (SC) once daily 5 days a week for up to 6 weeks.

Drug: Aldesleukin

Interventions

Aldesleukin DRUG

High-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses). Receive low-dose aldesleukin subcutaneously (SC) once daily 5 days a week for up to 6 weeks

Cohort I - high dose Aldesleukin; Cohort II - low dose Aldesleukin

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. The diagnosis of metastatic melanoma and positivity for gp100 will be confirmed by the Laboratory of Pathology of the the National Cancer Institute (NCI).
• Patients must be refractory to high dose aldesleukin treatment if they are medically eligible to receive it. Patients with noncutaneous melanoma are not required to be refractory to high dose aldesleukin.
• gp100:154-162 reactive peripheral blood lymphocytes derived from a
• leukapheresis.
• HLA-A\*0201 positive.
• Greater than or equal to 18 years of age.
• Willing to practice birth control during treatment and for four months after receiving the preparative regimen.
• 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 for the high dose aldesleukin cohort or ECOG 0, 1 or 2 for the low dose aldesleukin cohort.
• Hematology:
• Absolute neutrophil count greater than 1000/mm\^3 without support of filgrastim
• Normal white blood cell (WBC) (greater than 3000/mm\^3).
• Hemoglobin greater than 8.0 g/dl

You may not qualify if:

• 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 required.
• For patients receiving high dose IL-2 only: 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).
• 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.
• The following patients will be excluded from the high-dose IL-2 arm (but will be eligible for the low-dose arm):
• History of coronary revascularization or ischemic symptoms
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
• Documented LVEF of less than or equal to 45% tested in patients with:
• Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
• Age greater than or equal to 60 years old
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/yrs of 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 (4)

• 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

• Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.

  PMID: 17200963 BACKGROUND

• Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001 May 17;411(6835):380-4. doi: 10.1038/35077246.

  PMID: 11357146 BACKGROUND

• Wang A, Chandran S, Shah SA, Chiu Y, Paria BC, Aghamolla T, Alvarez-Downing MM, Lee CC, Singh S, Li T, Dudley ME, Restifo NP, Rosenberg SA, Kammula US. The stoichiometric production of IL-2 and IFN-gamma mRNA defines memory T cells that can self-renew after adoptive transfer in humans. Sci Transl Med. 2012 Aug 29;4(149):149ra120. doi: 10.1126/scitranslmed.3004306.

  PMID: 22932225 DERIVED

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

• Joohee Sul, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2008
• First Posted: April 24, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 19, 2015
• Results First Posted: January 22, 2013

Record last verified: 2015-09

Locations

US (1)