Clinical trial • Phase I/II • Oncology

GOLCADOMIDE for Follicular B-cell non-Hodgkin's lymphoma | Primary central nervous system lymphoma | Marginal zone lymphoma | Diffuse large B-cell lymphoma | Mantle cell lymphoma

Phase I/II trial of GOLCADOMIDE for Follicular B-cell non-Hodgkin's lymphoma | Primary central nervous system lymphoma | Marginal zone lymphoma | Diffuse…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Follicular B-cell non-Hodgkin's lymphoma | Primary central nervous system lymphoma | Marginal zone lymphoma | Diffuse large B-cell lymphoma | Mantle cell lymphoma
Trial Stage
Phase I/II
Drug Modality
Small molecule | Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
25-07-2024
First CTIS Authorization Date
23-09-2024

Trial design

Randomised, open-label, valemetostat tosylate (oral film-coated tablet) — dose/schedule not specified-controlled, adaptive Phase I/II trial in Denmark, France, Spain and others.

Randomised
Yes
Open Label
Yes
Comparator
Valemetostat Tosylate (oral film-coated tablet) — dose/schedule not specified
Adaptive
True, includes dose-escalation design with DLT evaluation period to define Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D); multiple combination cohorts and cohort expansions described.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
234

Eligibility

Recruits 234 No vulnerable population selected. Subjects must be ≥18 years and provide informed consent. No paediatric/assent provisions are described..

Pregnancy Exclusion
Agree to follow the CC-99282 Pregnancy Prevention Plan (PPP)
Vulnerable Population
No vulnerable population selected. Subjects must be ≥18 years and provide informed consent. No paediatric/assent provisions are described.

Inclusion criteria

  • {"criterion_text":"- Subject is ≥18 years of age at the time of signing the informed consent form (ICF).\n- Subject has a history of NHL (including DLBCL, FL, MZL, MCL and PCNSL) with relapsed or refractory disease\n- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.\n- Subjects must have the following laboratory values: a. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L or ≥ 1 x 10^9/L in case of documented bone marrow involvement, without growth factor support for 7 days (14 days if pegfilgastrim) b. Hemoglobin (Hgb) ≥ 8 g/dL c. Platelets (plt) ≥ 75 x 10^9/L or ≥ 50 x 10^9/L in case of documented bone marrow involvement, without transfusion for 7 days d. Serum bilirubin ≤ 1.5 x ULN (upper limit of normal). e. AST/SGOT and ALT/SGPT ≤ 2.5X ULN f. Estimated serum creatinine clearance of > 30 mL/min using the Cockcroft-Gault equation or directly determined from the 24-hour urine collection method or using the modification of diet in renal disease (MDRD) formula. For Cohort G and H, estimated serum creatinine clearance of ≥ 45 mL/min using the Cockcroft-Gault equation or directly determined from the 24-hour urine collection method or using the modification of diet in renal disease (MDRD) formula.\n- Agree to follow the CC-99282 Pregnancy Prevention Plan (PPP)"}

Exclusion criteria

  • {"criterion_text":"- Subject has life expectancy ≤ 2 months.\n- Subjects who have aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid potential life-threatening consequences (eg, due to tumor location).\n- Subject has received prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting investigational product(s), whichever is shorter.\n- Subject has symptomatic CNS involvement of disease (does not apply to PCNSL subjects in Part B).\n- Subject is on chronic systemic immunosuppressive therapy or corticosteroids (eg, prednisone or equivalent not to exceed 10 mg per day within the last 14 days) or subjects with clinically significant graft versus- host disease (GVHD).\n- Subject had prior autologous SCT ≤ 3 months prior to starting investigational product(s) and any treatment-related toxicity is unresolved (grade > 1).\n- Subject had prior allogeneic SCT with either standard or reduced intensity conditioning ≤ 6 months prior to starting investigational product(s) and any treatment-related toxicity is unresolved (grade > 1)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- AEs including treatment-emergent adverse events (TEAEs), laboratory assessments, vital signs, ECG results, ECOG performance status, LVEF assessments, and physical examinations.","definition_or_measurement_approach":"Safety assessments including monitoring and recording AEs/TEAEs, laboratory tests, vital signs, ECGs, ECOG performance status, LVEF assessments and physical examinations."}
  • {"endpoint_text":"- Recommended Phase 2 Dose (RP2D) and dosing Schedule(s): Dose limiting toxicities (DLTs), and Maximum Tolerated Dose (MTD) during the DLT evaluation period; establish the RP2D and optimal schedule of CC-99282 as monotherapy and in combination with rituximab obinutuzumab, tafasitamab or valemetostat ± rituximab.","definition_or_measurement_approach":"DLT evaluation during the defined DLT assessment period to determine MTD and establish RP2D and optimal dosing schedules for monotherapy and combination regimens."}

Secondary endpoints

  • {"endpoint_text":"- Preliminary efficacy: Determined by the Lugano Classification for NHL response criteria including: Objective response rate (ORR), any complete response (CR) or partial response (PR) as best response; Time to response (TTR); Duration of response (DoR); Progression free survival (PFS) and overall survival (OS); Additional DOR, PFS and OS for subjects treated for 6 cycles with CC-99282 + rituximab who discontinue due to achieving CR (Cohort I)","definition_or_measurement_approach":"Efficacy assessed using Lugano Classification for NHL response (ORR, CR, PR), TTR, DoR, PFS, OS; subgroup analyses including subjects treated for 6 cycles with CC-99282 + rituximab (Cohort I)."}
  • {"endpoint_text":"- Preliminary efficacy in PCNSL: Determined using the modified International PCNSL Collaborative Group (IPCG) criteria including: Objective response rate (ORR); Time to response (TTR); Duration of response (DoR); Progression free survival (PFS) and overall survival (OS)","definition_or_measurement_approach":"Efficacy in PCNSL assessed using modified IPCG criteria (ORR, TTR, DoR, PFS, OS)."}

Recruitment

Planned Sample Size
234
Recruitment Window Months
95
Consent Approach
Informed consent obtained from participants (subjects ≥18). Subject Information Sheets and Informed Consent Forms are available in multiple country-specific languages (English, French, Spanish, Italian). Pregnancy-related information and a Pregnancy Prevention Plan are provided; partner/pregnant participant information/ICF documents exist.

Geography

Total Number Of Sites
23
Total Number Of Participants
204

Denmark

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
25-06-2025
Processing Time Days
315
Number Of Sites
3
Number Of Participants
27

Sites

Site Name
Sygehus Lillebaelt Vejle Sygehus
Department Name
Department of Hematology
Principal Investigator Name
Michael Clausen
Principal Investigator Email
michael.roost.clausen@rsyd
Contact Person Name
Michael Clausen
Contact Person Email
michael.roost.clausen@rsyd
Site Name
Aarhus Universitetshospital
Department Name
Department of Hematology
Principal Investigator Name
Judit Jørgensen
Principal Investigator Email
judijoer@rm.dk
Contact Person Name
Judit Jørgensen
Contact Person Email
judijoer@rm.dk
Site Name
Rigshospitalet
Department Name
Hematology
Principal Investigator Name
Anna Caroline Riley
Principal Investigator Email
anna.caroline.riley@regionh.dk
Contact Person Name
Anna Caroline Riley
Contact Person Email
anna.caroline.riley@regionh.dk

France

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
25-06-2025
Processing Time Days
315
Number Of Sites
9
Number Of Participants
115

Sites

Site Name
Oncopole Claudius Regaud
Department Name
IUCT Oncopole
Principal Investigator Name
Pierre Bories
Principal Investigator Email
bories.pierre@iuct-oncopole.fr
Contact Person Name
Pierre Bories
Contact Person Email
bories.pierre@iuct-oncopole.fr
Site Name
Hospices Civils De Lyon
Department Name
Hematology
Principal Investigator Name
Emmanuel Bachy
Principal Investigator Email
emmanuel.bachy@chu-lyon.fr
Contact Person Name
Emmanuel Bachy
Contact Person Email
emmanuel.bachy@chu-lyon.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hematology
Principal Investigator Name
Catherine Thieblement
Principal Investigator Email
catherine.thieblemont@aphp.fr
Contact Person Name
Catherine Thieblement
Contact Person Email
catherine.thieblemont@aphp.fr
Site Name
Institut Bergonie
Department Name
Hematology
Principal Investigator Name
Fontanet Bijou
Principal Investigator Email
f.bijou@bordeaux.unicancer.fr
Contact Person Name
Fontanet Bijou
Contact Person Email
f.bijou@bordeaux.unicancer.fr
Site Name
Institut Gustave Roussy
Department Name
early therapeutic innovation
Principal Investigator Name
Vincent Ribrag
Principal Investigator Email
vincent.ribrag@gustaveroussy.fr
Contact Person Name
Vincent Ribrag
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Clinical Hematology
Principal Investigator Name
Guillaume Cartron
Principal Investigator Email
g-cartron@chu-montpellier.fr
Contact Person Name
Guillaume Cartron
Contact Person Email
g-cartron@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Blood disease
Principal Investigator Name
Franck Morschhauser
Principal Investigator Email
franck.morschhauser@chru-lille.fr
Contact Person Name
Franck Morschhauser
Site Name
Centre Henri Becquerel
Department Name
Oncology
Principal Investigator Name
Fabrice Jardin
Principal Investigator Email
fabrice.jardin@chb.unicancer.fr
Contact Person Name
Fabrice Jardin
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hematology
Principal Investigator Name
Corinne Haioun
Principal Investigator Email
corinne.haioun@aphp.fr
Contact Person Name
Corinne Haioun
Contact Person Email
corinne.haioun@aphp.fr

Spain

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
26-06-2025
Processing Time Days
316
Number Of Sites
6
Number Of Participants
34

Sites

Site Name
Hospital Universitario De Salamanca
Department Name
Oncologia
Principal Investigator Name
Norma Gutierrez
Principal Investigator Email
normagu@usal.es
Contact Person Name
Norma Gutierrez
Contact Person Email
normagu@usal.es
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Oncologia
Principal Investigator Name
Antonio Rueda-Dominaguez
Principal Investigator Email
rueda.dominguez@gmail.com
Contact Person Name
Antonio Rueda-Dominaguez
Contact Person Email
rueda.dominguez@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncologia
Principal Investigator Name
Laura Abril
Principal Investigator Email
labril@iconcologia.net
Contact Person Name
Laura Abril
Contact Person Email
labril@iconcologia.net
Site Name
Hospital Universitario La Paz
Department Name
Oncologia
Principal Investigator Name
Pilar Gomez
Principal Investigator Email
pilargp84@gmail.com
Contact Person Name
Pilar Gomez
Contact Person Email
pilargp84@gmail.com
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncologia
Principal Investigator Name
Daniel Morillo
Principal Investigator Email
dmorillo@startmadrid.com
Contact Person Name
Daniel Morillo
Contact Person Email
dmorillo@startmadrid.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncologia
Principal Investigator Name
Cecilia Carpio
Principal Investigator Email
ccarpio@vhio.net
Contact Person Name
Cecilia Carpio
Contact Person Email
ccarpio@vhio.net

Italy

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
12-11-2025
Processing Time Days
455
Number Of Sites
5
Number Of Participants
28

Sites

Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Dipartimento Malattie Oncologiche ed ematologiche
Principal Investigator Name
Vittorio Stefani
Principal Investigator Email
vittorio.stefoni2@unibo.it
Contact Person Name
Vittorio Stefani
Contact Person Email
vittorio.stefoni2@unibo.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Department Name
S.C. Ematologia Oncologica
Principal Investigator Name
Silvia Ferrari
Principal Investigator Email
s.ferrari@asst-pg23.it
Contact Person Name
Silvia Ferrari
Contact Person Email
s.ferrari@asst-pg23.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
UOC Ematologia I
Principal Investigator Name
Luca Arcaini
Principal Investigator Email
l.arcaini@smatteo.pv.it
Contact Person Name
Luca Arcaini
Contact Person Email
l.arcaini@smatteo.pv.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
SC Ematologia
Principal Investigator Name
Antonio Pinto
Principal Investigator Email
a.pinto@istitutotumori.na.it
Contact Person Name
Antonio Pinto
Contact Person Email
a.pinto@istitutotumori.na.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Dipartimento Ematologia, Oncologia e Medicina Molecolare
Principal Investigator Name
Erika Ravelli
Principal Investigator Email
erika.ravelli@ospedaleniguarda.it
Contact Person Name
Erika Ravelli

Sponsor

Primary sponsor

Full Name
Celgene Corp.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Programming (and other sponsor duties indicated by codes 10, 11, 6)
Name
Endpoint Clinical Inc.
Responsibilities
IVRS30 – treatment randomization
Name
QPS LLC
Responsibilities
TCR clonality

Third parties

  • {"country":"United States","full_name":"QPS LLC","duties_or_roles":"TCR clonality","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"ex vivo T-Cell stimulation analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"database, kits, logistics, management, storage","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS30 – treatment randomization","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Programming (plus other duties indicated by sponsor duty codes 10,11,6)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Golcadomide
Active Substance
GOLCADOMIDE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
1
Investigational Product Name
Valemetostat Tosylate
Active Substance
VALEMETOSTAT TOSILATE
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
1
Orphan Designation
Yes
Investigational Product Name
RITUXIMAB
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
2
Combination Treatment
Yes

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