A study to evaluate how safe is CC-220, how is the body affected by CC-220, and a preliminary idea on how CC-220 works, when given alone or together with a medicine to treat cancer, in patients with lymphoma that is not responding to treatment or that has re-appeared.
- Conditions
- Relapsed or refractory lymphoma including the following subtypes:Aggressive B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and classical Hodgkin lymphoma.MedDRA version: 20.0Level: HLGTClassification code 10025319Term: Lymphomas Hodgkin's diseaseSystem Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10034623Term: Peripheral T-cell lymphoma unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061275Term: Mantle cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10023699Term: Large B-cell lymphoma subtype primary mediastinal (Thymic) large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-000354-10-DE
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 232
Subjects must satisfy the following criteria to be enrolled in the study:
1. Is = 18 years of age at the time of signing the informed consent form (ICF).
2. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to 2016 WHO classification including:
a. Cohort A and Cohort D: all subtypes including B-cell, T-cell and NK-cell NHL, and cHL.
b. Cohort B: all B-cell NHL.
c. Cohort C: FL Grade 1-3a and MZL.
d. Cohort D: aggressive B-cell lymphoma and FL grade 1-3a
e. Cohort E: aggressive B-cell lymphoma, Grade 3b FL and PMBCL.
f. Cohorts F and G: FL Grade 1 to 3a .
3. Relapsed or refractory disease according to the following definitions:
a. Aggressive B-cell lymphoma including transformed indolent NHLs to
aggressive B-cell lymphoma: after at least 2 prior lines of therapy one of
which must include an anti-CD20 monoclonal antibody and anthracycline
containing regimen.
b. FL and MZL: following at least 2 prior lines of systemic therapy (being previously exposed to at least 1 anti-CD20 mAb and 1 alkylating agent).
c. MCL: following at least 2 prior lines of therapy including at least 1 immunochemotherapy and 1 BTK inhibitor.
d. PTCL: following at least 2 prior lines of therapy OR after 1 prior line of standard therapy and being not eligible for any other approved regimen.
e. cHL: following at least 2 prior systemic lines of therapy and previously exposed to brentuximab vedotin and anti-PD1.
f. All other subtypes: following at least 2 prior lines of therapy.
g. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of the indication).
4. Subjects must not be eligible for any other approved treatment for
their underlying lymphoma as assessed by the Investigator
5. Must have measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and 1 bi-dimensionally measurable (> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification (Cheson, 2014). Site of measurable disease cannot be previously irradiated.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
7. Must have the following laboratory values:
a. Absolute neutrophil count (ANC) = 1.5 x 109/L or = 1.0 x 109/L
b. Hemoglobin (Hb) = 8 g/dL.
c. Platelets (Plt) = 75 x 109/L or = 50 x 109/L
d. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) = 2.5 x ULN.
e. Serum total bilirubin = 1.5 ULN except in cases of Gilbert’s syndrome, then = 3.0 ULN.
f. Estimated serum creatinine clearance of = 50 mL/min.
8. All subjects must:
a. Have an understanding that the study drug could have a potential teratogenic risk.
b. Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
9. Females of childbearing potential (FCBP1) must have 2 negative pregnancy tests as verified by the Investigator prior to starting study treatment and must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
10. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 year
The presence of any of the following will exclude a subject from enrollment:
1. Any significant medical condition, active infection (including SARSCoV-
2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- A patient who is excluded for SARS-CoV-2 infection could be rescreened.
- In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the clinical trial physician, there are no sequelae that
would place the participant at a higher risk receiving investigational treatment.
- Additionally, a patient who is currently in another interventional trial for Coronavirus infectious disease 2019 (COVID-19) may not participate in the clinical trial until the protocol-specific washout period is achieved.
- Testing to exclude asymptomatic SARS-CoV-2 prior to enrollment should follow local standard practice.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Life expectancy = 3 months.
4. Diagnosis of lymphoblastic lymphoma.
5. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid potential life-threatening consequences (eg, due to tumor location).
6. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F) or obinutuzumab (for Cohorts C and G).
7. Prior therapy with the cereblon-modulating drug CC-99282.
8. Chronic systemic immunosuppressive therapy or corticosteroids.
9. Prior ASCT = 3 months prior to starting CC-220 or > 3 months AND with unresolved, Grade > 1, treatment-related toxicity.
10. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning = 6 months prior to starting CC-220 or > 6 months with unresolved, Grade > 1, treatment-related toxicity.
11. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or obinutuzumab.
12. Known allergy to thalidomide, pomalidomide or lenalidomide.
13. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.
14. Major surgery = 2 weeks prior to starting CC-220.
15. Peripheral neuropathy = Grade 2 (NCI CTCAE v5.0).
16. Documented or suspected CNS involvement of disease.
17. Subject with clinically significant cardiac disease.
18. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
19. Known chronic active hepatitis B.
20. History of other malignancy, unless the subject has been free of the disease for = 3 years; exceptions to the = 3-year time limit include history of incidental histologic finding of prostate cancer or prostate cancer that has been treated with curative intent.
21. Subject received live attenuated vaccines or live COVID-19 vaccines within 30 days prior to initiation of study treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To define the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CC-220 (iberdomide), alone and in combination with rituximab or obinutuzumab, in subjects with relapsed or refractory (R/R) lymphoma.;Secondary Objective: - To determine the safety and tolerability of CC-220 alone and in combination with rituximab or obinutuzumab in subjects with R/R lymphoma.<br>- To characterize the pharmacokinetics (PK) of CC-220 alone and in combination with rituximab or obinutuzumab.<br>- To evaluate the preliminary efficacy of CC-220 alone and in combination with rituximab or obinutuzumab in R/R lymphoma.;Primary end point(s): MTD and RP2D: Frequency of DLTs to define MTD and establish the RP2D of CC-220 as monotherapy and in combination with rituximab or obinutuzumab;Timepoint(s) of evaluation of this end point: DLT evaluation period defined from first CC-220 dose in C1 to C2D1 predose during Part 1
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1 - Safety and tolerability: Type, frequency and severity of adverse events (AEs) and relationship of AEs to investigational product.<br>2 - PK: C max, C trough, AUC(TAU), Tmax, CLT/F for CC-220<br>3 - Efficacy: Best ORR, CRR, TTR, DOR, PFS, OS, according to 2014 IWG Response criteria for NHL;Timepoint(s) of evaluation of this end point: 1 - Safety: From first dose to 28 days after last subject discontinues study treatment<br>2 - PK: C1D15<br>3 - Every 2 cycles through cycle 6, then every 3 cycles during treatment period and then every 6 months. <br> From enrollment date to end of study