T-Cell Infusion, Aldesleukin, and Utomilumab in Treating Patients With Recurrent Ovarian Cancer

Phase I/Ib Study of Adoptive Cellular Therapy Using Autologous IL-21-Primed CD8+ Tumor Antigen-Specific T Cells in Combination With Utomilumab (PF-05082566) in Patients With Platinum Resistant Ovarian Cancer

This phase I/Ib trial studies the side effects and best dose of utomilumab and how well it works with CD8-positive T-lymphocyte (T-cell infusion) and aldesleukin in treating patients with ovarian cancer that has come back. Aldesleukin may stimulate white blood cells to kill ovarian cancer cells. Giving white blood cells (T-cells) that have been activated by a vaccine with aldesleukin may kill more tumor cells. Immunotherapy with utomilumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving T-cell infusion with aldesleukin and utomilumab may work better in treating patients with ovarian cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Ovarian Carcinoma; HLA-A*0201 Positive Cells Present; COL6A3 Positive; PRAME Positive
• Intervention / Treatment: Drug: Cyclophosphamide; Procedure: Leukapheresis; Biological: Aldesleukin; Biological: Utomilumab; Drug: CD8-Positive T-Lymphocyte

Detailed Description

PRIMARY OBJECTIVES:

I. Assess the safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, utomilumab, an agonistic anti-CD137 antibody, in patients with platinum-resistant ovarian cancer.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without utomilumab.

SECONDARY OBJECTIVES:

I. Evaluate the anti tumor effect of adoptively transferred central memory-type CTL targeting ovarian cancer antigens as measured by best overall response rate (BORR) and progression free survival (PFS).

OUTLINE: This is a dose escalation study of utomilumab.

Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV) on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin subcutaneously (SC) every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 3, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histopathologic documentation (must be performed or reviewed at MD Anderson) of recurrent high grade epithelial ovarian cancer.
• At least one prior line of platinum-based chemotherapy (subjects are eligible for enrollment and leukapheresis while still platinum-sensitive, however, they must have developed platinum resistant disease for treatment (turnstile 2).
• Tumor expressing PRAME and/or COL6A3.
• Expression of HLA-A*0201.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival of greater than 16 weeks.
• Willing and able to give informed consent.
• Hemoglobin >= 9.0 g/dL.
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (>=1000 per mm^3).
• Platelet count >= 75 x 10^9/L (>=100,000 per mm^3).
• Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless diagnosed with Gilbert's syndrome.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5x ULN.
• Serum creatinine clearance (CL) >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
• Subjects must either be of non-reproductive potential (i.e., post-menopausal by history: >= 50 years old and no menses for >=1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped.
• {Turnstile 2} Subjects must have platinum resistant disease (progression on a platinum-containing regimen or recurrence within 180 days of last dose of platinum-containing chemotherapy). Subjects that are not platinum resistant but are deemed not to be candidates for platinum-based chemotherapy due to prior significant allergic reaction may participate with principal investigator (PI) approval.
• {Turnstile 2} Bi-dimensionally measurable disease by radiographic imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan).
• {Turnstile 2} At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy, radiotherapy or major surgery. At least 6 weeks for bevacizumab.
• {Turnstile 2} Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible.

Exclusion Criteria:

• Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 60% of normal or carbon monoxide diffusing capacity (DLco) (corrected [corr] for hemoglobin [Hgb]) < 55% will be excluded.
• Significant cardiovascular abnormalities including any one of the following: Congestive heart failure, Clinically significant hypotension, symptoms of coronary artery disease, presence of cardiac arrhythmias on electrocardiography (EKG) requiring drug therapy; or patients with a history of cardiovascular disease. (Patients with the above will undergo a cardiac evaluation which can include a stress test and/or echocardiography. Results of this evaluation will be considered before excluding patients on the basis of cardiovascular abnormalities). Subjects with evidence of stress-induced cardiac ischemia or ejection fraction less than 55% will be excluded.
• History of central nervous system (CNS) metastasis.
• Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
• {Turnstile 2} Participation in another clinical study with an investigational product administered during the last 28 days.
• {Turnstile 2} Receipt of the last dose of previous chemotherapy, hormonal, or biologic treatment for ovarian, fallopian tube, or primary peritoneal cancer in the last 28 days (in the last 6 weeks for bevacizumab).
• {Turnstile 2} Current or prior use of immunosuppressive medication within 28 days before enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• {Turnstile 2} Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1.
• History of allogeneic organ transplant.
• Unresolved partial or complete small or large bowel obstruction.
• {Turnstile 2} Receipt of live attenuated vaccination within 30 days prior to enrollment or within 30 days of planned lymphodepletion.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events.
• Active viral hepatitis.
• Confirmed human immunodeficiency virus (HIV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (T-cell infusion, aldesleukin, utomilumab); Patients undergo leukapheresis. Patients then receive cyclophosphamide IV on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin SC every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Procedure: Leukapheresis; Undergo leukapheresis; Other Names: Leukocytopheresis; Therapeutic Leukopheresis; Biological: Aldesleukin; Given IV; Other Names: Proleukin; 125-L-Serine-2-133-interleukin 2; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; Biological: Utomilumab; Given IV; Other Names: PF-05082566; PF 05082566; PF 5082566; PF-2566; Drug: CD8-Positive T-Lymphocyte; Given IV; Other Names: CD8 Cell; CD8 Lymphocyte; CD8 Lymphocytes; CD8+ T Cell; CD8+ T Lymphocyte; CD8+ T Lymphocytes; CD8+ T-Lymphocyte; CD8-Positive Lymphocyte; CD8-Positive Lymphocytes; CD8-Positive T-Lymphocytes; T8 Cell; T8 Cells; T8 Lymphocyte; T8 Lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer	Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives	will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Anti Tumor Effect of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens as Measured by Best Overall Response Rate (BORR) and Progression Free Survival (PFS).	Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives	will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amir A Jazaeri, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2018
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Antirheumatic Agents; Sensory System Agents; Antiviral Agents; Analgesics, Non-Narcotic; Analgesics; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anti-HIV Agents; Anti-Retroviral Agents; Cyclophosphamide; Antibodies, Monoclonal; Immunoglobulin G; Aldesleukin; Interleukin-2
• Other Study ID Numbers: 2016-0400 (Other Identifier: M D Anderson Cancer Center); NCI-2018-01034 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No