Clinical Trials /

Phase II Trial of Nivolumab for Pediatric and Adult Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma, for Evaluation of Response in Patients With Progressive Disease (Cohort 1) or as Consolidative Immunotherapy in Patients in Complete Remission After Relapse (Cohort 2)

NCT03703050

Description:

Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Anaplastic Large Cell Lymphoma, ALK-Positive
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial of Nivolumab for Pediatric and Adult Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma, for Evaluation of Response in Patients With Progressive Disease (Cohort 1) or as Consolidative Immunotherapy in Patients in Complete Remission After Relapse (Cohort 2)
  • Official Title: Phase II Trial of Nivolumab for Pediatric and Adult Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma, for Evaluation of Response in Patients With Progressive Disease (Cohort 1) or as Consolidative Immunotherapy in Patients in Complete Remission After Relapse (Cohort 2)

Clinical Trial IDs

  • ORG STUDY ID: 2018-001447-31
  • SECONDARY ID: 2018/2706
  • NCT ID: NCT03703050

Conditions

  • Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma

Interventions

DrugSynonymsArms
Nivolumab cohort 1Cohort 1
Nivolumab cohort 2Cohort 2

Purpose

Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPopulation: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin).
  • Nivolumab cohort 1
Cohort 2ExperimentalPopulation: patients with a relapsed/refractory ALCL, having achieved CR with a treatment including ALK-inhibitor or Brentuximab vedotin of at least 2 months and for whom HSCT is considered for their consolidation therapy. In this case, nivolumab would be considered as consolidative immunotherapy instead as HSCT.
  • Nivolumab cohort 2

Eligibility Criteria

        Inclusion Criteria:

        All criteria from I-1 to I-10 are required for all patients, in addition of the
        cohort-specific criteria

        I-1. Histologically confirmed evidence of relapsed/refractory ALK+ ALCL. If biopsy could
        not be performed, relapsed/refractory status should be confirmed by molecular analysis
        whenever possible (increase of MRD quantitative PCR at 2 consecutive measures qualifying
        for a significant increase according to the same reference laboratory, with clinical signs
        and symptoms suggestive of progressing disease). In this case, relapsed/refractory status
        must be reviewed and confirmed by the international coordinating investigator.

        I-2. Age at inclusion > 6 months I-3. No washout needed, but patients must have recovered
        from acute toxic effects of all prior therapy before enrollment into the study. A short
        course of steroids is allowed at the beginning of Nivolumab if it is clinical indicated

        I-4. Adequate organ function:

          -  Peripheral absolute neutrophil count (ANC) ≥750/μL in patients without bone marrow
             involvement and ≥500/μL in patients with bone marrow involvement (unsupported)

          -  Platelet count ≥75,000/μL in patients without bone marrow involvement and 50 000 in
             patients with bone marrow involvement (unsupported)

          -  Hemoglobin ≥8.0 g/dL (transfusion is allowed)

          -  Serum creatinine ≤1.5 x upper limit of normal (ULN) for age

          -  Total bilirubin ≤1.5 x ULN in patients without liver involvement and < 2.5 ULN in
             patients with liver involvement

          -  Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤3 x ULN in
             patients without liver involvement and < 5 ULN in patients with liver involvement

          -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤3 x ULN
             in patients without liver involvement and < 5 ULN in patients with liver involvement
             I-5. Performance status: Karnofsky performance status (for patients >12 years of age)
             or Lansky Play score (for patients ≤12 years of age) ≥ 40%.

        I-6. Able to comply with the scheduled disease management (treatment and follow-up), and
        with the management of toxicity I-7. Females of childbearing potential must have a negative
        serum β-HCG pregnancy test within 24 hours prior to initiation of treatment. Sexually
        active women of childbearing potential must agree to use acceptable and appropriate
        contraception during the study and for at least 5 months after the last study treatment
        administration. Sexually active males patients must agree to use condom during the study
        and for at least 7 months after the last study treatment administration. I-8. Written
        informed consent from parents/legal representative, patient, and age-appropriate assent
        before any study-specific screening procedures are conducted according to local, regional
        or national guidelines.

        I-9. Patient affiliated to a social security regimen or beneficiary of the same according
        to local requirements.

        I-10. Patients will prior allogeneic HSCT may be included if clinically indicated (see
        non-inclusion criteria regarding prior allogeneic HSCT). In this case, study inclusion must
        be confirmed by the international coordinating investigator.

        Cohort 1:

        For being enrolled in Cohort 1, all criteria from C1.I-1 to C1.I-2 are required, in
        addition of I-1 to I-10 criteria C1.I-1. Measurable progressive disease with at least one
        lesion measuring more than 1.5 cm and/or evaluable disease on PET-CT C1.I-2. Previous
        treatment including chemotherapy and ALK inhibitor or brentuximab vedotin, if available.

        Cohort 2:

        For being enrolled in Cohort 2, all criteria from C2.I-1 to C2.I-2 are required, in
        addition of I-1 to I-10 criteria C2.I-1. Complete response (disappearance of all disease
        except for possible detection of MRD in blood and/or bone marrow) with an on-going
        treatment of at least 2 months with ALK inhibitor or brentuximab vedotin, if available
        combined or not with chemotherapy C2.I-2. High-risk relapsed/refractory ALK+ ALCL for whom
        an hematopoietic stem cell transplantation is considered after CR

        Exclusion Criteria:

        E-1. Patients with prior allogeneic HSCT less than 3 months before study inclusion E-2.
        Patients with prior allogeneic HSCT and any active graft versus host disease (GVHD) and/or
        any prior grade 3 or 4 GVHD according to International Bone Marrow Transplant Registry
        (ITBMR) E-3. Previous organ transplantation E-4. Significant hemophagocytosis in bone
        marrow, spleen, lymph nodes, or liver must be discussed with the Coordinating Sponsor
        before inclusion E-5. Presence of any ≥ CTCAE grade 2 treatment-related toxicity with the
        exception of alopecia, fatigue and peripheral neuropathy.

        E-6. History or evidence of severe uncontrolled illness that contra-indicates use of an
        investigational drug, or places the patient at unacceptable risk from treatment
        complications E-7. History or evidence of severe acute or chronic infection unless fully
        healed at least four weeks prior to screening E-8. Known human immunodeficiency virus (HIV)
        infection E-9. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C
        virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.

        E-10. History or evidence of any auto-immune disease. Subjects with vitiligo, type I
        diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring
        hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected
        to recur in the absence of an external trigger are permitted to enroll.

        E-11. Subjects with another pathology requiring systemic treatment with either
        corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
        medications within 14 days of study drug administration. Inhaled or topical steroids, and
        adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence
        of active autoimmune disease.

        E-12. Known hypersensitivity to any component of the products (study drug or ingredients)
        E-13. Concurrent administration of any other antitumor therapy E-14. Clinically
        significant, uncontrolled heart disease (including history of any cardiac arrhythmias,
        e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12
        months of screening).

        E-15. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the
        study drug E-16. Pregnant or breast-feeding female patient E-17. Patient under guardianship
        or deprived of his liberty by a judicial or administrative decision, patients under
        safeguards of justice or incapable of giving its consent, patients undergoing psychiatric
        care under duress E-18. Participation in another clinical study with an investigational
        product during the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Cohort 1 - Best objective response rate (Complete Response + Partial Response)
Time Frame:within the first 24 weeks
Safety Issue:
Description:In case of PET-positive residual masses after 24 weeks of induction treatment, a resection/biopsy must be performed by week 24. A residual mass proven to be pathologically negative for disease after resection or limited biopsy is considered as CR after discussion with the Coordinating investigator.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gustave Roussy, Cancer Campus, Grand Paris

Last Updated