Relapsing/Refractory ALK+ Anaplastic Large Cell LymphomaPhase 2NIVO-ALCLNCT03703050
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)
A Phase 2 study testing Nivolumab cohort 1 and Nivolumab cohort 2 in people with Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 13 sites in 3 countries.
Trial summary
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma
- What is being tested?
- Nivolumab cohort 1 and Nivolumab cohort 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 2 Jan 2019to Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
France11 sites
CHU Bordeaux Hopital Pellegrin
Bordeaux, 33076
CHU Bordeaux
Bordeaux
CHU Mondor
Créteil
Centre Oscar Lambret
Lille
Centre Léon Berard Lyon
Lyon, 69008
Hôpital Trousseau
Paris, Paris, 75012
Hôpital Saint Louis
Paris, 75010
CHU Toulouse Hopital des enfants
Toulouse, 31059
IUC Toulouse
Toulouse, 31059
CHU de nancy
Vandœuvre-lès-Nancy, 54500
Gustave Roussy
Villejuif, Val de Marne, 94805
United Kingdom1 site
Women'S and Children'S Nhs Foundation Trust
Birmingham
About this study
Official title: 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
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab
Read the detailed description
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab
Cohort 1:
Population: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin).
Primary endpoint: ORR = best objective response rate (CR+PR) within the first 24 weeks, assessed according to adapted Lugano 2014 response criteria for Lymphoma.
Design: A one-stage phase II trial with unacceptable ORR = 40% and promising ORR = 70%. 12 eligible and evaluable patients are required.
Cohort 2 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 for 24 months would be considered as consolidative immunotherapy instead as HSCT.
Primary endpoint: progression-free survival (PFS) A PFS rate ≤ 50% will be considered as unacceptable. Design: A four-stage phase II trial with unacceptable PFS rate = 50% and promising PFS rate = 75%. A maximum of twenty-six patients will be included: 4 at the 1st and 2nd stages, 8 at the 3rd stage and 10 at the 4th stage.
No more than one third of the included patients must have received more than 12 months of ALK inhibitor or brentuximab. Thus, the inclusion of these patients will be closed after 8 patients.
- Being tested
- Nivolumab cohort 1, Nivolumab cohort 2
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab cohort 1Drug
Also called OpDIVO
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
Nivolumab cohort 2Drug
Also called opdivo
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
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Population: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin). Receives: 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. Receives: Drug: Nivolumab cohort 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2018
- Study start2 Jan 2019
- Primary completionApr 2026 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing/Refractory ALK+ Anaplastic Large Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Véronique Minard, Pr, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03703050
- Sponsor's protocol ID
- 2018-001447-31
- Other IDs
- 2018/2706, 2018
- Acronym
- NIVO-ALCL
- Status last verified
- Mar 2026
- First submitted
- 9 Oct 2018
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03703050
- Acronym / sponsor ID
- NIVO-ALCL / 2018-001447-31
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- 2 Jan 2019 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 11 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab
Detailed description
Prospective, non-randomized, single arm phase II trial with 2 cohorts of ALK+ ALCL treated with nivolumab
Cohort 1:
Population: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin).
Primary endpoint: ORR = best objective response rate (CR+PR) within the first 24 weeks, assessed according to adapted Lugano 2014 response criteria for Lymphoma.
Design: A one-stage phase II trial with unacceptable ORR = 40% and promising ORR = 70%. 12 eligible and evaluable patients are required.
Cohort 2 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 for 24 months would be considered as consolidative immunotherapy instead as HSCT.
Primary endpoint: progression-free survival (PFS) A PFS rate ≤ 50% will be considered as unacceptable. Design: A four-stage phase II trial with unacceptable PFS rate = 50% and promising PFS rate = 75%. A maximum of twenty-six patients will be included: 4 at the 1st and 2nd stages, 8 at the 3rd stage and 10 at the 4th stage.
No more than one third of the included patients must have received more than 12 months of ALK inhibitor or brentuximab. Thus, the inclusion of these patients will be closed after 8 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Nivolumab cohort 1Population: relapsed/refractory ALK+ ALCL with progressive disease after treatment (including chemotherapy and ALK inhibitor and/or brentuximab vedotin). |
| Cohort 2 | Experimental | Drug: Nivolumab cohort 2Population: 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. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- 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
- Peripheral absolute neutrophil count (ANC) ≥750/μL in patients without bone marrow involvement and ≥500/μL in patients with bone marrow involvement (unsupported)
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab cohort 1Also: OpDIVOInduction: 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 | Drug | Cohort 1 |
| Nivolumab cohort 2Also: opdivoInduction: 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 | Drug | Cohort 2 |
Primary outcome
Cohort 1 - Best objective response rate (Complete Response + Partial Response)
Time frame: within the first 24 weeks
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.
Cohort 2 - Progression Free Survival
Time frame: up to 12 months
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Véronique Minard, Pr principal investigator
Gustave Roussy, Cancer Campus, Grand Paris
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab cohort 1 and Nivolumab cohort 2 in people with Relapsing/Refractory ALK+ Anaplastic Large Cell Lymphoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort 1 - Best objective response rate (Complete Response + Partial Response) (time frame: within the first 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.