Informations générales (source: ClinicalTrials.gov)
Phase II Trial of Nivolumab for Pediatric and Adult Relapsing/Refractory 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
Interventional
Phase 2
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
janvier 2019
septembre 2025
29 août 2025
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL
treated with nivolumab
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | V�ronique MINARD-COLIN | 10/04/2024 13:23:23 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Armand Trousseau-La Roche Guyon | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Berard Lyon - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Centre Oscar Lambret - Lille - France | Contact (sur clinicalTrials) | ||||
| CHU Bordeaux - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| CHU Bordeaux Hopital Pellegrin - 33076 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| CHU de nancy - 54500 - Vandœuvre-lès-Nancy - France | Contact (sur clinicalTrials) | ||||
| CHU Mondor - Créteil - France | Contact (sur clinicalTrials) | ||||
| CHU Toulouse Hopital des enfants - 31059 - Toulouse - France | Contact (sur clinicalTrials) | ||||
| Hôpital Saint Louis - 75010 - Paris - France | Contact (sur clinicalTrials) | ||||
| IUC Toulouse - 31059 - Toulouse - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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
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
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