ALCL
Conditions
Interventions
Cohort 1
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: nivo
Sponsors
Gustave Roussy
Eligibility
Age
No minimum to 64 Years
Inclusion criteria
Inclusion 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 12 years of age) or Lansky Play score (for patients = 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. Acceptable contraception is listed in Appendix 5. 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 evalua
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 PETpositive 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. Cohort 2 3-year PFS PFS is defined as the time since the inclusion in the trial, to the first event among relapse (see definition below) and death, whatever the cause of death Definition of relapse: In case of developpement of new lesion(s) based on CT scan and/or MRI and/or PET-CT: - In patients with clinical deterioration, a biopsy should be performed whenever possible, in order to obtain histological confirmation of the relapse. Additional MRD assessment (with quantitave PCR) is also recommended. In patient in whom a biopsy is not feasisible, an increase of MRD quantitative PCR at 2 consecutive measures qualifying for a significant increase according to the same reference laboratory, along with clinical signs and symptoms suggestive of progressing disease and new lesion(s) on imagings will be considered as a relapse. In this case, relapsed status must be reviewed and confirmed by the international coordinating investigator. - In patients without clinical deterioration (scheduled assessment imaging), a confirmatory CT scan and/or MRI (+ optional PET-CT), along with MRD assessment (with quantitave PCR) and a biopsy (whenever possible), should be performed 4 weeks later on, in order to confirm or not the relapse. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 (first met of these criteria of measurement), evaluated according to adapted Lugano 2014 Criteria for Malignant Lymphoma, until confirmed progression, or death. - Progression-free survival, defined as the time since the inclusion in the trial, to the first event among confirmed progression, relapse, and death, whatever the cause of death. - Confirmed progression is defined according to Lugano 2014 Criteria for Malignant Lymphoma. However: - In patients with clinical deterioration, a biopsy should be performed whenever possible, in order to obtain histological confirmation of the progression. Additional MRD assessment (with quantitave PCR) is also recommended. An increase of MRD quantitative PCR at 2 consecutive measures qualifying for a significant increase according to the same reference laboratory, along with clinical signs and symptoms suggestive of progressing disease and progression on imagings will be considered as a progression/relapse. In this case, progressive/relapse status must be reviewed and confirmed by the international coordinating investigator. - In patients without clinical deterioration (scheduled assessment imaging), a confirmatory CT scan and/or MRI (+ optional PET-CT), along with MRD assessment (with quantitave PCR) and a biopsy (whenever possible), should be performed 4 weeks later on, in order to confirm or not the progression/relapse. See chapt 7.3 for details - Overall survival, defined as the time since the inclusion in the trial to death, whatever the cause of death. - Minimal residual disease (MRD) measured by quantitative PCR for NPM1-ALK in the blood at various time-points (see Table 1 to Table 4) Cohort 2 - Overall survival, defined as the time since the inclusion in the trial to death, whatev | — |
Countries
Netherlands
Outcome results
None listed