High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI

NCT01266603 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0113NCI-2011-00282
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if high-dose interleukin-2 (HDIL-2), when given in combination with recMAGE-A3 + AS15 ASCI (Antigen-Specific Cancer Immunotherapeutic), can help to control unresectable or metastatic melanoma in patients whose tumor tissue has the MAGE-A3 protein. The safety of this drug combination will also be studied. Researchers will also use samples of the original tumor or metastatic tissue (for example, lymph nodes or liver or lung) that are collected during screening to study if response to the study drug is related to the genes in the tissue.

Conditions

Melanoma

Keywords

Metastatic Melanoma; Unresectable Melanoma; HDIL-2; Interleukin-2; IL-2; Aldesleukin; Proleukin; recMAGE-A3 + AS15; ASCI; recMAGE-A3; Recombinant MAGE-A3 protein; recMAGE-A3 + AS15 ASCI; MAGE-A3; MAGE-A3 ASCI

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  To evaluate the objective response rate induced by the concurrent administration of HDIL-2 and recMAGE-A3 + AS15 ASCI in patients with MAGE-A3-positive, unresectable or metastatic melanoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Until disease progression or up to 3 years & 9 months

Secondary Outcomes (2)

• Rate of SAEs

  Until treatment completed or up to 3 years & 9 months

• Progression-free Survival

  Until treatment completed or up to 3 years & 9 months.

Study Arms (1)

HDIL-2 + recMAGE-A3 + AS15

EXPERIMENTAL

HDIL-2 720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. recMAGE-A3 300 μg plus 420 μg of CpG7909 (a part of the Adjuvant System AS15) by intermuscular injection within 24 hours from first dose of HDIL-2.

Drug: HDIL-2; Biological: recMAGE-A3 + AS15

Interventions

HDIL-2 DRUG

720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle.

Also known as: Interleukin-2, IL-2, Aldesleukin, Proleukin

HDIL-2 + recMAGE-A3 + AS15

recMAGE-A3 + AS15 BIOLOGICAL

300 μg plus 420 μg of CpG7909 (a part of the Adjuvant System AS15) by intermuscular injection within 24 hours from first dose of HDIL-2.

Also known as: Recombinant MAGE-A3 Protein, recMAGE-A3 + AS15 ASCI, MAGE-A3, MAGE-A3 ASCI

HDIL-2 + recMAGE-A3 + AS15

Eligibility Criteria

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

You may qualify if:

• STEP 1 Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
• Male or female patient with histologically proven, measurable unresectable or metastatic cutaneous melanoma
• Patient is \>/= 18 years of age.
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for MAGE-A3 expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or liver lesion. Archival FFPE tumor tissue can be provided for the MAGE-A3 screening test, as long as the FFPE tumor tissue was obtained from a biopsy or resection and no systemic chemotherapy, immunotherapy or targeted therapy has been received by the patient between the tumor collection and the MAGE-A3 screening test. Fresh tumor tissue in RNAlater must be also available for gene signature testing. Patients must have at least one biopsiable cutaneous, subcutaneous, lymph node lesion, The tumor sample should be preferably from the same lesion as the FFPE tumor tissue. Cutaneous lesions must measure \>/= 4mm and lymph nodes, subcutaneous, lung or liver lesions must measure \>/= 1cm.
• STEP 2 ANA (antinuclear antibody) titer \< 1:80
• STEP 2 The patient's tumor shows expression of MAGE-A3 gene.
• ECOG performance status of 0 or 1.
• WBC \>/= 3000/mm\^3 and Hemoglobin \>/= 9 g/dl
• Platelet count \>/= 100,000/mm\^3.
• Normal AST and ALT except for patients with liver metastases, in which serum ALT and AST \</= 2.5 X upper limit of normal (ULN) will be permitted.
• Creatinine \</= 1.5 mg/dL
• Normal total bilirubin except for patients with liver metastases, in which total bilirubin \</= 1.5 X ULN will be permitted (patients with Gilbert's syndrome must have a total bilirubin less that 3.0 mg/dL).
• LDH \</= 2 X ULN
• Stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) with estimated ejection fraction \>50% within 6 months of signing consent form
• Pulmonary function tests showing FEV1 \> 65% or FVC \> 65% of predicted within 6 months of signing consent form

You may not qualify if:

• The patient has at any time received systemic chemotherapy, immunotherapy or targeted therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant setting, as long as this was performed at least 4 weeks before first study treatment administration).
• Brain metastasis or history of brain metastasis.
• Any types of melanoma other than cutaneous, i.e. ocular or mucosal .
• The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.
• Patients with a history of second malignancies are eligible provided that they have been free of recurrence from secondary malignancy for at least 3 years, does not include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.
• The patient has a history of an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis, and inflammatory bowel disease or an antinuclear antibody (ANA) titer \> 1:80.
• The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational compound.
• The patient has a family history of congenital or hereditary immunodeficiency.
• Known to be positive for viral hepatitis B or C (HBsAg or Anti HCV) or HIV (HIV antibodies) Patients should have a negative test within 6 months of starting treatment.
• Systemic steroid therapy, steroid-containing compounds or any other immunosuppressive agents or to be used for more than 7 consecutive days (at a dose of prednisone or equivalent of \>/= 0.125 mg/kg/day).
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures. Each patient will be evaluated by the principal investigator or his designee.
• The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. Each patient will be evaluated by the principal investigator or his designee.
• Initiation of another anti-cancer therapy.
• For female patients: the patient is pregnant or lactating.
• WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• McQuade JL, Homsi J, Torres-Cabala CA, Bassett R, Popuri RM, James ML, Vence LM, Hwu WJ. A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma. BMC Cancer. 2018 Dec 19;18(1):1274. doi: 10.1186/s12885-018-5193-9.

  PMID: 30567529 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Interleukin-2; aldesleukin; MAGEA3 protein, human

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Michael A Davies, BA,MD,PHD/Melanoma Medical Oncology
• Organization: U T MD Anderson Cancer Center

MDavies@mdanderson.org

713-792-3454

Study Officials

• Wen-Jen Hwu, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 24, 2010
• Study Start: February 22, 2011
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: February 19, 2020
• Results First Posted: February 19, 2020

Record last verified: 2020-02

Locations

US (1)