Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma
Condition: Peripheral T Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Nivolumab; cabiralizumab
Intervention description: Nivolumab 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. Nivolumab will be delivered intravenously at a fixed dose of 240 mg on day 1 of 14 day cycles.; Cabiralizumab is a recombinant, humanized Immunoglobulin G4 (IgG4) monoclonal antibody that binds to human colony stimulating factor 1 receptor (CSF1R; c-fms). Cabiralizumab will be delivered intravenously at a dosage of 4 mg/kg on day 1 of 14 day cycles.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility 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.

          -  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.