Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma

Overview

About this study

The primary objective of Part 1 of this study is to define the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CC-220 in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone given in 21-day treatment cycles (R-CHOP-21) and CC99282 in combination with R-CHOP-21 in subjects with previously untreated, high risk (International Prognostic Index [IPI] 3 to 5), a-BCL.

The primary objective of Part 2 of this study is to further evaluate the safety and tolerability associated with CC-220 and CC-99282 at the RP2D in combination with R-CHOP-21 in subjects with previously untreated, high-risk (IPI 3 to 5), a-BCL.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

4. Participants must have measurable disease defined by at least one FDG-avid lesion
for FDGavid 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 syndrome, then
≤ 5.0 mg/dl

6. Estimated serum creatinine clearance of ≥ 50 mL/min

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.

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. Chronic systemic immunosuppressive therapy or corticosteroids

8. 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 scan (MUGA) or echocardiogram (ECHO)

9. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must
have recovered from any clinically significant effects of recent surgery.

10. Any condition causing inability to swallow tablets.

11. Known seropositivity for or active viral infection with human immunodeficiency
virus (HIV)

12. Known chronic active hepatitis B (hepatitis B 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

13. 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.

14. Hypersensitivity to the active substance or to murine proteins, or to any of the
other excipients of rituximab.

15. Known hypersensitivity to any component of CHOP regimen.

16. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Grzegorz Nowakowski, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Javier Munoz, M.D., M.B.A.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Muhamad Alhaj Moustafa, M.D., M.S.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions