This study has been transitioned to CTIS with ID 2023-503715-14-00 check the CTIS register for the current data. Part A: To characterize the safety, tolerability, and define the MTD or RP2D for the combination of relatlimab + nivolumab in pediatric…
ID
Source
Brief title
Condition
- Lymphomas Hodgkin's disease
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1/Part A- Dose-limiting toxicities (DLTs), Maximum Tolerated Dose/Recommended
Phase 2 Dose; (MTD/RP2D), and incidences of Adverse Events (AEs), Serious
Adverse Events (SAEs), AEs leading to discontinuation, deaths and laboratory
abnormalities
2/Part A- maximum observed serum concentration (Cmax), trough observed
concentration (Ctrough), time to maximum concentration
(Tmax), and area under the curve within a dosing interval (AUC(TAU)) for
relatlimab
3/Part B- Complete Metabolic Response (CMR) rate
Secondary outcome
1/Part B: Incidences of AEs, SAEs, AEs leading to discontinuation, deaths, and
laboratory abnormalities
2/Part B: Overall Response Rate (ORR)
Background summary
Participants with recurrent/relapsed or refractory cHL and NHL have limited
treatment options. There is currently no consensus or identified best salvage
regimen in pediatric and adolescent patients with recurrent/relapsed or
refractory (R/R) cHL. There is little consistency in therapeutic approaches,
and there is no formal recommendation on the best approach for this poor
prognostic subgroup; new treatment options are needed.
Study objective
This study has been transitioned to CTIS with ID 2023-503715-14-00 check the CTIS register for the current data.
Part A: To characterize the safety, tolerability, and define the MTD or RP2D
for the combination of relatlimab + nivolumab in pediatric participants less
than 18 years of age with R/R cHL and NHL.
Part A: To characterize the PK of relatlimab for the combination of relatlimab
+ nivolumab in pediatric participants less than 18 years of
age with R/R cHL and NHL.
Part B: To assess the preliminary efficacy of relatlimab + nivolumab based on
the RP2D from part A in participants less than or equal to 30
years old with cHL (Cohort 1).
Study design
CA224069 is an open-label, Phase 1/2 clinical trial of relatlimab + nivolumab
in children, adolescents, and young adults with R/R cHL and NHL. Part A will
encompass safety and dose determination of relatlimab + nivolumab. Part B will
be composed of an expansion cohort of cHL (Cohort 1) and an exploratory
assessment in NHL (Cohort 2).
Participants will continue treatment until progressive metabolic disease (PMD),
death, unacceptable toxicity, symptomatic deterioration, the Investigator*s
decision to discontinue treatment, the participant*s decision to discontinue
treatment or withdraw consent, for a maximum
of 2 years of study treatment, the participant is lost to follow-up, or study
termination by the Sponsor.
Intervention
Flat-dosing (AF) cohort will include: participants >= 12 years old who weigh >=
40 kg:
• D = Relatlimab 160 mg + nivolumab 480 mg intravenous (IV) Q4W (A1F); if the
starting dose
is found to be not tolerated, then the relatlimab dose will be decreased as
follows:
• D-1 = Relatlimab 80 mg + nivolumab 480 mg IV Q4W (A2F).
Age/weight-based dosing (AW) cohort will include: participants >= 12 years old
and with a
weightwho weigh < 40 kg and/or participants < 12 years old irrespective of
weight:
• D = Relatlimab 2 mg/kg (max 160 mg) + nivolumab 6 mg/kg (max 480 mg) Q4W
(A1W); if
the starting dose is found to be not tolerated, then the relatlimab dose will
be decreased as
follows:
• D-1 = Relatlimab 1 mg/kg (max 80 mg) with nivolumab 6 mg/kg (max 480 mg) Q4W
(A2W).
Study burden and risks
The study contains a screening phase, treatment phase and a follow-up phase.
We anticipate a 2 year treatment phase for patients with a 3 year follow up
period.
Visits can last 5-6 hours.
The subject will have to undergo several examinations, tests and/or procedures
before, during and after his/her treatment. Please referto the procedure table
in the ICF and Schedule of Assessment of the protocol for more information.
In addition, questions are asked about the medical history, demographics and
eligibilty questions
Subjects will also be tested for HIV and hepatitis. Female patients will be
tested for pregnancy .
The anticipated total duration of the study is approximately 5 years.
Possible side effects that are already known are described in the
Investigator's Brochure and the patient informed consent form.
Chaussée de la Hulpe 185
Brussels 1170
BE
Chaussée de la Hulpe 185
Brussels 1170
BE
Listed location countries
Age
Inclusion criteria
- Male and female participants less than 18 years of age (Part A), and less
than or equal to
30 years of age (Part B) with R/R cHL (Cohort 1) and NHL (Cohort 2).
- Participants with pathologically confirmed high-risk R/R cHL, after
non-response to or failure
of first-line standard therapy prior to a definitive therapy (eg. HDCT/ASCT).
- high-risk for cHL is defined by early relapse, extranodal disease or B
symptoms at relapse,
extensive disease where radiation therapy was contraindicated at relapse,
and/or relapse in
a prior radiation field.
- Participants with pathologically confirmed R/R NHL after failure or
non-response to first-line
therapy, including but not limited to primary mediastinal B-cell lymphoma,
diffuse large B-cell
lymphoma (DLBCL), mediastinal gray zone lymphoma (MGZL), anaplastic large cell
lymphoma (ALCL), or peripheral T-cell lymphoma (PTCL).
- high-risk for NHL is defined as applicable (eg, in young adults) by a
second-line therapy
age-adjusted International Prognostic Index score of >= 2 factors.
- The participant*s current disease state must be R/R to standard therapy.
- Participants must have measurable PET positive disease in both cHL and NHL
cohorts.
Exclusion criteria
- Aggressive B-cell lymphomas subtypes including Burkitt lymphoma (BL),
lymphoblastic
lymphoma, and NK/T-cell lymphoma/leukemia.
- Primary CNS lymphoma of the brain or spinal cord, and secondary CNS lymphoma
(ie, from
systemic non-Hodgkin lymphoma) involving the brain, spinal cord, or with
leptomeningeal
seeding.
- Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4
antibody, or any
other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways,
with the exception of anti-PD(L)-1 targeted therapies.
- Prior treatment with LAG-3-targeted agents.
- Participants with prior autologous stem cell transplantation (HDCT/ASCT).
- Participants with a history of allogeneic bone marrow transplantation.
- Participants with clinically significant systemic illnesses unrelated to the
cancer as judged by
the investigators, which would compromise the participant*s ability to tolerate
the study
treatment.
- Participants with autoimmune disease.
- Participants who are pregnant or breastfeeding.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-503715-14-00 |
| EudraCT | EUCTR2021-000493-29-NL |
| ClinicalTrials.gov | NCT05255601 |
| CCMO | NL82628.041.23 |