Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT03927105
• Recruitment Status: Recruiting
• First Posted: April 25, 2019
• Last Update Posted: October 15, 2019
• Sponsor: Big Ten Cancer Research Consortium
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Big Ten Cancer Research Consortium

Study Description

Brief Summary:

A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma

Condition or disease	Intervention/treatment	Phase
Peripheral T Cell Lymphoma	Drug: Nivolumab; Drug: cabiralizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 33 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma
• Actual Study Start Date: April 25, 2019
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Nivolumab + Cabiralizumab; Nivolumab 240mg IV + Cabiralizumab 4mg/kg on day 1 of every 14 day cycle.

Drug: Nivolumab; Nivolumab (also referred to as BMS-936558 or MDX1106) is a human monoclonal antibody (HuMAb; immunoglobulin G4 [IgG4]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens.; Other Name: Opdivo; Drug: cabiralizumab; Nivolumab (also referred to as BMS-936558 or MDX1106) is a human monoclonal antibody (HuMAb; immunoglobulin G4 [IgG4]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens.; Other Names: BMS-936558; MDX1106

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) at four months (LYRIC Criteria) [ Time Frame: 4 months ]
   Overall Response Rate as determined by LYRIC (LYmphoma Response to Immunomodulatory therapy Criteria) criteria, at four months
2. Complete Response Rate(CRR) at four months [ Time Frame: 4 months ]
   Complete response rate, as determined by LYRIC criteria, at four months

Secondary Outcome Measures :

1. Overall response at four months by (LUGANO 2014) criteria [ Time Frame: four months ]
   Overall response, as determined by LUGANO 2014 criteria, at four months
2. Complete Response Rate at four months (LUGANO 2014) criteria [ Time Frame: four months ]
   Complete Response Rate, as determined by LUGANO 2014 criteria, at four months
3. Progression-Free Survival (PFS) [ Time Frame: 60 Months ]
   Progression-Free Survival will be measured from date of enrollment until the criteria for disease progression (PD) is met or death occurs. Subjects who have not progressed will be right-censored at the date of the last disease evaluation.
4. Disease Control Rate (DCR) [ Time Frame: 60 Months ]
   The proportion of all subjects with stable disease (SD) for 8 weeks, PR, or CR.
5. Duration of Response (DOR) [ Time Frame: 60 Months ]
   Duration of Response measured from the time that measurement criteria are met for CR or PR (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).
6. Time to Next Treatment (TNT) [ Time Frame: 60 Months ]
   Time to next treatment (TNT) is defined as the time from the date of enrollment to the institution of next treatment.
7. Summarize Adverse Events [ Time Frame: 60 Months ]
   Assess and summarize adverse events (AEs) using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent for clinical trial enrollment and mandatory consent for any biopsies as well as HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2.
• Histological confirmation of peripheral T-cell lymphoma (PTCL) except adult T-cell leukemia/lymphoma (ATLL).
• Documented disease progression after receiving at least two prior therapeutic regimen including brentuximab vedotin in patients with CD30 positive disease (defined as >10% CD30 positive cells).
• Prior cancer treatment must be completed at least 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ grade 1 or baseline. Systemic steroids at a dose less than the equivalent of 10 mg/day of prednisone and inhaled, nasal, and topical steroids are permitted. Adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease are permitted. Treatment with a short course of steroids (< 5 days) up to 7 days prior to study registration is permitted. Intermittent dexamethasone for the treatment of nausea/emesis is also permitted.
• Demonstrate adequate organ function as defined in the table in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin) performed at screening and within 24 hours of first dose of investigational treatment. See Section 5.4.1 of the protocol for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 5 months after the last dose of investigational product. See Section 5.4.1 of the protocol for methods of contraception.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drugs and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. See Section 5.4.1 of the protocol for methods of contraception.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

• PTCL histology consistent with ATLL.
• A history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study.
• Active infection requiring systemic therapy
• Recent (<100 days) autologous stem cell transplant, or previous allogeneic stem cell transplant.
• Known positive test for HIV. NOTE: HIV screening is not required.

• History of any chronic hepatitis as evidenced by the following:

  • Positive test for hepatitis B surface antigen
  • Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR]).
  • NOTE: Participants with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion criterion.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Previous malignancies (except non-melanoma skin cancers and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
• Prior treatment with cabiralizumab (or other CSF1R pathway inhibitors).
• Prior treatment with nivolumab or other medications within the checkpoint blockade family.
• Any unregulated nutritional or herbal supplement or recreational drug within 2 weeks prior to registration which, in the opinion of the study investigator, has the potential to cause hepatic injury.
• Concomitant use of statins for treatment of hypercholesterolemia. Statins are allowed only if the patient is on a stable dose for over 3 months prior to study registration and is in a stable status without CK elevations.
• Use of any prescription or over-the-counter acid controllers within 4 weeks prior to study drug administration except those medications approved by the sponsor investigator.
• Non-oncology vaccine therapies for prevention of infectious diseases (e.g., human papilloma virus vaccine) within 4 weeks of study registration. The inactivated seasonal influenza vaccine can be given to patients before treatment and while on therapy without restriction. Influenza vaccines containing live virus or other clinically indicated vaccinations for infectious diseases (i.e., pneumovax, varicella, etc.) may be permitted, but must be discussed with the sponsor investigator and may require a study drug washout period before and after administration of vaccine.
• Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and Tween 80 (polysorbate 80)
• History of allergy to any components of cabiralizumab or nivolumab

• Active, known, or suspected autoimmune disease.

  • NOTE: Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the sponsor investigator.
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
• Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels.

• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:

  • Myocardial infarction or stroke/transient ischemic attack within the past 6 months
  • Uncontrolled angina within the past 3 months
  • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
  • History of other clinically significant heart disease (e.g., cardiomyopathy (impaired LVEF), congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)
  • Cardiovascular disease-related requirement for daily supplemental oxygen therapy.

Contacts and Locations

Contacts

Contact: Ryan Wilcox, MD, PhD; 734-615-1482; rywilcox@med.umich.edu

Contact: Donna Sullivan; 317-634-5842 ext 40; dsullivan@hoosiercancer.org

Locations

United States, Michigan

University of Michigan Comprehensive Cancer Center; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Ryan Wilcox, M.D. 734-615-1482 rwilcox@med.umich.edu

Contact: Sumana Devata 734-615-7813 sdevata@med.umich.edu

United States, Wisconsin

Unviersity of Wisconsin; Recruiting

Madison, Wisconsin, United States, 53705

Contact: Erin Clements 608-265-2857 eclements@wisc.edu

Principal Investigator: Kari Wisinski, MD

Sponsors and Collaborators

Big Ten Cancer Research Consortium

Bristol-Myers Squibb

Investigators

• Principal Investigator: Ryan Wilcox, MD, PhD; University of Michigal Rogel Cancer Center

More Information

• Responsible Party: Big Ten Cancer Research Consortium
• ClinicalTrials.gov Identifier: NCT03927105 History of Changes
• Other Study ID Numbers: BTCRC-HEM16-085
• First Posted: April 25, 2019
• Last Update Posted: October 15, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents