Clinical Trials /

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

NCT03927105

Description:

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

Related Conditions:
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-HEM16-085
  • NCT ID: NCT03927105

Conditions

  • Peripheral T Cell Lymphoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab + Cabiralizumab
cabiralizumabBMS-936558, MDX1106Nivolumab + Cabiralizumab

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + CabiralizumabExperimentalNivolumab 240mg IV + Cabiralizumab 4mg/kg on day 1 of every 14 day cycle.
  • Nivolumab
  • cabiralizumab

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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) at four months (LYRIC Criteria)
Time Frame:4 months
Safety Issue:
Description:Overall Response Rate as determined by LYRIC (LYmphoma Response to Immunomodulatory therapy Criteria) criteria, at four months

Secondary Outcome Measures

Measure:Overall response at four months by (LUGANO 2014) criteria
Time Frame:four months
Safety Issue:
Description:Overall response, as determined by LUGANO 2014 criteria, at four months
Measure:Complete Response Rate at four months (LUGANO 2014) criteria
Time Frame:four months
Safety Issue:
Description:Complete Response Rate, as determined by LUGANO 2014 criteria, at four months
Measure:Progression-Free Survival (PFS)
Time Frame:60 Months
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:60 Months
Safety Issue:
Description:The proportion of all subjects with stable disease (SD) for 8 weeks, PR, or CR.
Measure:Duration of Response (DOR)
Time Frame:60 Months
Safety Issue:
Description: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).
Measure:Time to Next Treatment (TNT)
Time Frame:60 Months
Safety Issue:
Description:Time to next treatment (TNT) is defined as the time from the date of enrollment to the institution of next treatment.
Measure:Summarize Adverse Events
Time Frame:60 Months
Safety Issue:
Description:Assess and summarize adverse events (AEs) using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Big Ten Cancer Research Consortium

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