An early study to investigate a new medicine for Subjects with Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 May 2019 → ongoing

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Celgene Corporation United States

External identifiers

EU CT number

2024-515690-10-00

EudraCT number

2018-003235-29

WHO UTN

U1111-1224-5399

ClinicalTrials.gov

NCT03930953

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Dose response, Pharmacogenomic, Pharmacodynamic

1. To determine the safety and tolerability of CC-99282 alone and in combination with rituximab, obinutuzumab, tafasitamab, or valemetostat ± rituximab in subjects with R/R NHL
2. To define the maximum tolerated dose (MTD) and/or the recommended Phase 2 doses (RP2D) of CC-99282 as monotherapy or in combination with anti-lymphoma agents in subjects with R/R NHL

Secondary objectives 2

1. To characterize the pharmacokinetics (PK) of CC-99282 in plasma when administered alone or in combination with anti-lymphoma agents
2. To provide information on the preliminary efficacy of CC-99282 alone or in combination with rituximab, obinutuzumab, tafasitamab or valemetostat ± rituximab in R/R NHL

Conditions and MedDRA coding

Follicular B-cell non-Hodgkin's lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
2. Subject has a history of NHL (including DLBCL, FL, MZL, MCL and PCNSL) with relapsed or refractory disease
3. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
4. 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.
5. Agree to follow the CC-99282 Pregnancy Prevention Plan (PPP)

Exclusion criteria 7

1. Subject has life expectancy ≤ 2 months.
2. Subjects who have aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid potential life-threatening consequences (eg, due to tumor location).
3. 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.
4. Subject has symptomatic CNS involvement of disease (does not apply to PCNSL subjects in Part B).
5. 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).
6. Subject had prior autologous SCT ≤ 3 months prior to starting investigational product(s) and any treatment-related toxicity is unresolved (grade > 1).
7. 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 and secondary outcome measures (English text)

Primary endpoints 2

1. AEs including treatment-emergent adverse events (TEAEs), laboratory assessments, vital signs, ECG results, ECOG performance status, LVEF assessments, and physical examinations.
2. 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.

Secondary endpoints 2

1. 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)
2. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 5

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications