Ipilimumab and Local Radiation for Selected Solid Tumors

NCT01769222 | Terminated Phase 1 Results FDA Drug

• 4 other identifiers: IRB-25597NCI-2012-02988VAR00905136
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase 1-2 trial studies the side effects and best of dose ipilimumab when given together with local radiation therapy and to see how well it works in treating patients with recurrent melanoma, non-Hodgkin lymphoma, colon, or rectal cancer. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiation therapy uses high energy x rays to kill cancer cells. Giving monoclonal antibody therapy together with radiation therapy may be an effective treatment for melanoma, non-Hodgkin lymphoma, colon, or rectal cancer.

• The phase 1 component ("safety") of this study is ipilimumab 25 mg monotherapy.
• The phase 2 component ("treatment-escalation") of this study is ipilimumab 25 mg plus radiation combination therapy.

Conditions

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicity

  Safety as the percentage of patients in Phase 1 (ipilimumab monotherapy) of the study, who experienced dose-limiting toxicities (DLTs) or serious adverse events (SAEs), using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  4 weeks

Secondary Outcomes (5)

• Immune Response (Phase 2 Only)

  4 weeks

• Immune Response (Phase 2 Only)

  8 weeks

• Response Rate (Phase 2 Only)

  8 weeks

• Overall Survival (Phase 2 Only)

  Up to 5 years

• Duration of Response (Phase 2 Only)

  Up to 5 years

Study Arms (2)

Ipilimumab 25 mg (Phase 1)

EXPERIMENTAL

Participants receive ipilimumab intratumorally on Day 1

Biological: Ipilimumab

Ipilimumab 25 mg and radiation therapy (Phase 2)

EXPERIMENTAL

Participants receive ipilimumab intratumorally on Day 1 and undergo local radiation therapy (10 Gy/fraction) within 48 hours for at least 3 fractions

Biological: Ipilimumab; Radiation: Radiation therapy

Interventions

Ipilimumab BIOLOGICAL

Given intratumorally

Also known as: Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, Monoclonal antibody CTLA-4

Ipilimumab 25 mg (Phase 1); Ipilimumab 25 mg and radiation therapy (Phase 2)

Radiation therapy RADIATION

Undergo local radiation therapy, 10 Gy x 3 fractions

Also known as: Irradiation, Radiotherapy, Therapy, radiation

Ipilimumab 25 mg and radiation therapy (Phase 2)

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent
• Before any study procedures are performed, subjects (or their legally acceptable representatives) will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel
• Histologically confirmed malignancy
• In Phase 1, histologically confirmed melanoma.
• In Phase 2, histologically confirmed melanoma, non-Hodgkin lymphoma, or colorectal carcinoma
• Must have failed at least 1 systemic therapy or be intolerant to at least one prior systemic treatment
• Must have at least 2 lesions of evaluable size by modified World Health Organization (mWHO)/Cheson criteria; 1 of 2 lesions must be amenable to biopsy (core or fine needle aspirate) and intratumoral injection of up to 5 mL (diameter ≥ 10mm)
• Subjects with asymptomatic brain metastases are eligible; (systemic steroids should be avoided if possible, or the subject should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose)
• Must be at least 28 days since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of ≥ 16 weeks
• Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab
• White blood cell (WBC) ≥ 2000/uL (\~2 x 10\^9/L)
• Absolute neutrophil count (ANC) ≥ 1000/uL (\~0.5 x 10\^9/L)
• Platelets ≥ 75 x 10\^3/uL (\~75 x 10\^9/L)

You may not qualify if:

• Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis)
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
• Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
• A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist
• Concomitant therapy with any of the following: interleukin-2 (IL 2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids
• A history of AEs with prior IL-2 or Interferon will not preclude subjects from entering the current study
• Any investigational agents
• Immunosuppressive agents (unless required for treating potential AEs)
• Chronic systemic corticosteroids (unless required for treating treatment emergent AEs or required for management of signs or symptoms due to brain metastases, upon discussion with Bristol-Myers Squibb \[BMS\] medical monitor)
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness
• Women of childbearing potential (WOCBP) who:
• Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
• Have a positive pregnancy test at baseline, or

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Intraocular Lymphoma; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell, Peripheral; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Colonic Neoplasms; Lymphoma, T-Cell, Cutaneous; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Melanoma; Mycosis Fungoides; Sezary Syndrome; Rectal Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Hairy Cell; Leukemia, Large Granular Lymphocytic; Waldenstrom Macroglobulinemia

Interventions

Ipilimumab; CTLA-4 Antigen; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy; Eye Neoplasms; Neoplasms by Site; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Rectal Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: George Albert Fisher, MD
• Organization: Stanford University Medical Center

georgeaf@stanford.edu

650-725-9057

Study Officials

• George A. Fisher, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Phase 1 ipilimumab 25 mg safety only. Subsequent Phase 2 ipilimumab 25 mg and radiation combination (treatment-escalation) was not conducted.

Study Record Dates

• First Submitted: January 14, 2013
• First Posted: January 16, 2013
• Study Start: February 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: June 1, 2015
• Last Updated: January 24, 2024
• Results First Posted: March 3, 2017

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)