NIVOLUMAB for ALK-positive anaplastic large cell lymphoma (relapsed/refractory)

Inclusion criteria

• {"criterion_text":"- All criteria from I-1 to I-10 are required for all patients, in addition of the cohort-specific criteria"}
• {"criterion_text":"- I-9. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 (see Appendix 1 for criteria according to the age) Of note, the inclusion of patients who have received more than 12 months of ALK inhibitor or brentuximab will be closed after 8 patients"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- I-2. Age at inclusion > 6 months"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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 involvment - Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤3 x ULN in patients without liver involvement and < 5 ULN in patients with liver involvment - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤3 x ULN in patients without liver involvement and < 5 ULN in patients with liver involvment"}
• {"criterion_text":"- I-5. Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 40%."}
• {"criterion_text":"- I-6. Able to comply with the scheduled disease management (treatment and follow-up), and with the management of toxicity"}
• {"criterion_text":"- 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 male patients must agree to use condom during the study and for at least 7 months after the last study treatment administration. Acceptable contraception is listed in Appendix 5."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- E-1. Patients with prior allogeneic HSCT less than 3 months before study inclusion"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- E-12. Known hypersensitivity to any component of the products (study drug or ingredients)"}
• {"criterion_text":"- E-13. Concurrent administration of any other antitumor therapy"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- E-15. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug"}
• {"criterion_text":"- E-16. Pregnant or breast-feeding female patient"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- E-18. Participation in another clinical study with an investigational product during the study"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- E-3. Previous organ transplantation"}
• {"criterion_text":"- E-4. Significant hemophagocytosis in bone marrow, spleen, lymph nodes, or liver must be discussed with the Coordinating Sponsor before inclusion"}
• {"criterion_text":"- E-5. Presence of any ≥ CTCAE grade 2 treatment-related toxicities with the exception of alopecia, fatigue and peripheral neuropathy."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- E-7. History or evidence of severe acute or chronic infection unless fully healed at least four weeks prior to screening"}
• {"criterion_text":"- E-8. Known human immunodeficiency virus (HIV) infection"}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Cohort 1: Best objective response rate (CR+PR) within the first 24 weeks according to adapted Lugano 2014 Criteria for Malignant Lymphoma. 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.","definition_or_measurement_approach":"Response assessed per adapted Lugano 2014 Criteria for Malignant Lymphoma within first 24 weeks; PET-positive residual masses after 24 weeks require resection/biopsy; pathologically negative residual mass may be considered CR after coordinating investigator discussion."}
• {"endpoint_text":"- Cohort 2: PFS. 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).","definition_or_measurement_approach":"Progression-free survival defined as time from inclusion to first event among relapse or death (any cause)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: Cohort 1 -Time between the first dose of treatment and the confirmed CR/PR according to adapted Lugano 2014 Criteria for Malignant Lymphoma -Duration of response (CR/PR), defined as the time between the CR or PR according to adapted Lugano 2014 Criteria for Malignant Lymphoma (first met of these criteria) until confirmed progression or death  Best objective response rate (CR+PR) according to adapted Lugano 2014 Criteria for Malignant Lymphoma - Progression-free survival (PFS)","definition_or_measurement_approach":"Time to confirmed CR/PR per adapted Lugano 2014; duration of response from first CR/PR until confirmed progression or death; best objective response rate per adapted Lugano 2014; PFS as defined in protocol."}
• {"endpoint_text":"- Efficacy : Cohort 2 : Overall survival  PFS and OS in the subgroup of patients having received less than 12 months of ALK inhibitor or brentuximab  Minimal Residual Disease blood level at various time-points","definition_or_measurement_approach":"Overall survival and PFS measured; subgroup analyses for patients with <12 months prior ALK inhibitor or brentuximab; MRD blood level measured at specified timepoints."}
• {"endpoint_text":"- Safety in cohorts 1 and 2:  Acute toxicity (NCI-CTCAE v5) during induction treatment, during maintenance treatment, and one month after the end of treatment Long-term toxicity (toxicity during the off-therapy period up to 5 years after study inclusion)","definition_or_measurement_approach":"Safety assessed using NCI-CTCAE v5 for acute toxicity during treatment and up to one month post-treatment; long-term toxicity monitored up to 5 years after inclusion."}
• {"endpoint_text":"- Biology in cohorts 1 and 2:  Anti-ALK antibody blood level at various time-points  Biomarkers on tumor and its microenvironment, blood and bone marrow, including PDL1 and PDL2 expression, and tumor infiltrating lymphocytes and leucocytes populations/cytokines, at different time points.","definition_or_measurement_approach":"Biomarker assessments including anti-ALK antibody levels, PD-L1/PD-L2 expression, tumor and microenvironment markers, and immune cell/cytokine profiling at designated time points."}

France

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

25-09-2024

Processing Time Days

8

Number Of Sites

14

Number Of Participants

41

Denmark

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

25-09-2024

Processing Time Days

8

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France