Nivolumab for Pediatric and Adult Relapsing/Refractory ALK+, 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 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 2018-001447-312018/2706
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 13

Brief Summary

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

Conditions

Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Cohort 1 - Best objective response rate (Complete Response + Partial Response)

  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.

  within the first 24 weeks

• Cohort 2 - Progression Free Survival

  PFS is defined as the time since the inclusion in the trial to the first event among relapse and death (whatever the cause of death).

  up to 12 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

Population: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin).

Drug: Nivolumab cohort 1

Cohort 2

EXPERIMENTAL

Population: 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.

Drug: Nivolumab cohort 2

Interventions

Nivolumab cohort 1 DRUG

Induction: nivolumab 3 mg/kg (maximal unitary dose: 240 mg) iv Q2W until CR Evaluation of response as defined below, including biopsy in case of residual masses at Week 24 Maintenance: nivolumab 3 mg/kg (maximal unitary dose: 240 mg) Q4W Total duration of treatment (induction + maintenance) = 24 months

Also known as: OpDIVO

Cohort 1

Nivolumab cohort 2 DRUG

Induction: nivolumab 3 mg/kg iv Q2W for 4 doses (Wk0, Wk2, Wk4 and Wk6) Maintenance: nivolumab 3 mg/kg Q4W, for 25 doses, starting at Week 8 (14 days after the last induction dose) Total duration of treatment (induction + maintenance) = 24 months

Also known as: opdivo

Cohort 2

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-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.

You may not qualify if:

• 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-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

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (13)

Rigshospitalet

Copenhagen, Denmark

Location

Hôpital Trousseau

Paris, Paris, 75012, France

Location

Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

CHU Bordeaux Hopital Pellegrin

Bordeaux, 33076, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU Mondor

Créteil, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Berard Lyon

Lyon, 69008, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

CHU Toulouse Hopital des enfants

Toulouse, 31059, France

Location

IUC Toulouse

Toulouse, 31059, France

Location

CHU de nancy

Vandœuvre-lès-Nancy, 54500, France

Location

Women'S and Children'S Nhs Foundation Trust

Birmingham, United Kingdom

Location

MeSH Terms

Conditions

Recurrence

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Véronique Minard, Pr

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab, according to patient status after previous treatment (patients in progression, into the Cohort 1; patients in CR, into the Cohort 2)

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 11, 2018
• Study Start: January 2, 2019
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

FR (11); DK (1); GB (1)