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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04884035




Registration number
NCT04884035
Ethics application status
Date submitted
7/05/2021
Date registered
12/05/2021

Titles & IDs
Public title
Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma
Scientific title
A Phase 1b, Open Label, Global, Multicenter, Dose Determination, Randomized Dose Expansion Study to Determine the Maximum Tolerated Dose, Assess the Safety and Tolerability, Pharmacokinetics and Preliminary Efficacy of Iberdomide (CC-220) in Combination With R-CHOP-21 and CC-99282 in Combination With R-CHOP-21 for Subjects With Previously Untreated Aggressive B-cell Lymphoma
Secondary ID [1] 0 0
2020-005705-71
Secondary ID [2] 0 0
CC-220-DLBCL-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, B-Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CC-220
Treatment: Drugs - Rituximab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone
Treatment: Drugs - CC-99282
Treatment: Drugs - Polatuzumab vedotin
Treatment: Drugs - Rituximab

Experimental: Administration of CC-220 with R-CHOP-21 - CC-220 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Experimental: Administration of CC-99282 with R-CHOP-21 - CC-99282 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Experimental: Administration of CC-220 with polatuzumab-R-CHP - CC-220 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment

Experimental: Administration of CC-99282 with polatuzumab-R-CHP - CC-99282 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment


Treatment: Drugs: CC-220
CC-220 by mouth at the assigned dose starting on Day 1 for 14 consecutive days of the 21-day treatment cycle for 6 cycles of treatment.

Treatment: Drugs: Rituximab
Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion or 1400 mg (SC) subcutaneous (from Cycle 2) of a 21-day treatment cycle for up to a total of 6 cycles

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles

Treatment: Drugs: Doxorubicin
Doxorubicin 50 mg/m2 IV infusion on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles

Treatment: Drugs: Vincristine
Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) IV intravenous on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles

Treatment: Drugs: Prednisone
Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles

Treatment: Drugs: CC-99282
CC-99282 by mouth at the assigned dose starting on Day 1 for 7 consecutive days of the 21-day treatment cycle for 6 cycles of treatment.

Treatment: Drugs: Polatuzumab vedotin
Polatuzumab vedotin 1.8 mg/kg on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles

Treatment: Drugs: Rituximab
Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) - Part 1
Timepoint [1] 0 0
During the first 2 cycles of treatment (each cycle is 21 days)
Primary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D) - Part 1
Timepoint [2] 0 0
During the first cycle of treatment (each cycle is 21 days)
Primary outcome [3] 0 0
Safety and tolerability of CC-220 and CC-99282 at RP2D - Part 2
Timepoint [3] 0 0
From the first dose of any IP until 28 days after the last dose of IP
Primary outcome [4] 0 0
Maximum Tolerated Dose (MTD) - Part 2A
Timepoint [4] 0 0
During the first cycle of treatment (each cycle is 21 days)
Primary outcome [5] 0 0
Recommended Phase 2 Dose (RP2D) - Part 2A
Timepoint [5] 0 0
During the first cycle of treatment (each cycle is 21 days)
Secondary outcome [1] 0 0
Best overall response rate (ORR)
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Complete Metabolic Response Rate (CMRR)
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Time to Response (TTR)
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Duration of Response (DOR)
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Progression-free Survival (PFS)
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Pharmacokinetics - Cmax for CC-220
Timepoint [7] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days)
Secondary outcome [8] 0 0
Pharmacokinetics - Ctrough for CC-220
Timepoint [8] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Secondary outcome [9] 0 0
Pharmacokinetics - Tmax for CC-220
Timepoint [9] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Secondary outcome [10] 0 0
Pharmacokinetics - Cmax for CC-99282
Timepoint [10] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Secondary outcome [11] 0 0
Pharmacokinetics - Ctrough for CC-99282
Timepoint [11] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Secondary outcome [12] 0 0
Pharmacokinetics - Tmax for CC-99282
Timepoint [12] 0 0
At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days

Eligibility
Key inclusion criteria
* Participants 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. Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated, a-BCL according to 2016 WHO classification.
3. Participant has International Prognostic Index (IPI) score 0-5 in Part 1 and IPI 2-5 in Part 2. For the CELMoD and polatuzumab-R-CHP cohort, the subject must also have IPI score 0 to 5 in Part 2A and IPI 2 to 5 in Part 2B.
4. Participants must have measurable disease defined by at least one FDG-avid lesion for FDG-avid subtype and one 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).
5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
6. Participants must have the following laboratory values:

1. Absolute neutrophil count (ANC) = 1.5 x 109/L or = 1.0 x 109/L in case of documented bone marrow involvement (> 50% or tumor cells), without growth factor support for 7 days (14 days if peg-G-CSF)
2. Hemoglobin (Hb) = 8 g/dL
3. Platelets (PLT) = 75 x 109/L or = 50 x 109/L in case of documented bone marrow involvement (>50% or tumor cells), without transfusion for 7 days
4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamate pyruvic transaminase (ALT/SGPT) = 2.5 x upper limit of normal (ULN). In the case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be = 5.0 x ULN.
5. Serum total bilirubin = 2.0 mg/dL except in cases of Gilbert's syndrome, then = 5.0 mg/dl. Subjects receiving polatuzumab vedotin must have serum total bilirubin < 1.5 × ULN (26 µmol/L) (corresponding to mild degree as per National Cancer Institute Organ Dysfunction Working Group [NCI ODWG] criteria) except in cases of Gilbert's syndrome, then = 3.0 mg/dl (51 µmol/L).
6. Estimated serum creatinine clearance (CrCl) of = 50 mL/min using the modification of diet in renal disease (MDRD) formula.
7. All participants must:

1. Have an understanding that the study drug could have a potential teratogenic risk.
2. Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 or CC-99282 Pregnancy Prevention Plan for Participants in Clinical trials.
8. Females of childbearing potential (FCBP) must:

a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy.
9. Male participants must:

1. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* The presence of any of the following will exclude a participant from enrollment:

1. Any significant medical condition, active infection (including SARS-CoV-2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
3. Any other subtype of lymphoma.
4. Documented or suspected CNS involvement by lymphoma.
5. Persistent diarrhea or malabsorption = Grade 2 (NCI CTCAE v5.0), despite medical management.
6. Peripheral neuropathy = Grade 2 (NCI CTCAE v5.0).
7. Subjects with a history of progressive multifocal leukoencephalopathy.
8. Chronic systemic immunosuppressive therapy or corticosteroids
9. Impaired cardiac function or clinically significant cardiac disease, including any of the following:

a. Left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
10. Major surgery = 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.
11. Any condition causing inability to swallow tablets.
12. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
13. Known chronic active hepatitis B (hepatitis B virus surface antigen [HBsAg] positive and/or hepatitis B core antibody [anti-HBc] positive with viral DNA positive) or C (positive serology requiring treatment and/or with evidence of liver damage) infection
14. History of other malignancy, unless being free of the disease for = 3 years; exceptions to the = 3-year time limit include history of the following:

1. Localized nonmelanoma skin cancer
2. Carcinoma in situ of the cervix
3. Carcinoma in situ of the breast
4. Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis [TNM] staging system) or prostate cancer that has been treated with curative intent.
15. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or polatuzumab vedotin.
16. Known hypersensitivity to any component of CHOP/CHP regimen.
17. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/02/2026
Actual
Sample size
Target
174
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Local Institution - 501 - Adelaide
Recruitment hospital [2] 0 0
Local Institution - 503 - Perth
Recruitment hospital [3] 0 0
Local Institution - 502 - Waratah
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
WA 6000 - Perth
Recruitment postcode(s) [3] 0 0
NSW - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Greece
State/province [8] 0 0
Athens
Country [9] 0 0
Greece
State/province [9] 0 0
Patras
Country [10] 0 0
Greece
State/province [10] 0 0
Thessaloniki
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Poland
State/province [12] 0 0
Gdansk
Country [13] 0 0
Poland
State/province [13] 0 0
Krakow
Country [14] 0 0
Poland
State/province [14] 0 0
Poznan
Country [15] 0 0
Poland
State/province [15] 0 0
Slomniki
Country [16] 0 0
Poland
State/province [16] 0 0
Warsaw
Country [17] 0 0
Poland
State/province [17] 0 0
Wroclaw
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Málaga
Country [21] 0 0
Spain
State/province [21] 0 0
Salamanca
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taichung
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BMS Study Connect Contact Center www.BMSStudyConnect.com
Address 0 0
Country 0 0
Phone 0 0
855-907-3286
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
See Plan Description
Available to whom?
See Plan Description
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04884035