Phase II trial of nivolumab for pediatric and adult relapsing/refractory ALK+ 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)

Phase 2

• Conditions: ALCL; 10025321

• Registration Number: NL-OMON56001
• Lead Sponsor: Gustave Roussy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 2

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 <=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
involvement
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT
<=3 x ULN in patients without liver involvement and < 5 ULN in patients with
liver involvment
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. 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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified