A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas

Overview

About this study

The purpose of this study is to evaluate CC-220 alone, as well as in combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and have at least one measurable lesion according to Lugano 2014 classification. Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2 (Dose Expansion).

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:

  • Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • Is willing and able to adhere to the study visit schedule and other protocol requirements.
  • Consents to retrieve formalin-fixed paraffin-embedded (FFPE) archival tumor tissue, either in tumor blocks or sectioned/mounted specimens, if collected within the last year and if using in place of biopsy at screening.
  • Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to 2016 WHO classification including:
    • Cohort A and Cohort D: all subtypes including B-cell, T-cell and NK-cell NHL, and cHL;
    • Cohort B: all B-cell NHL;
    • Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and PMBCL;
    • Cohorts C, F and G: FL Grade 1 to 3a and MZL including extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma), nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma (SMZL).
  • Relapsed or refractory disease according to the following definitions:
    • Aggressive B-cell lymphoma: after at least 2 prior lines of therapy including R-CHOP-like regimen;
    • 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) and in need for treatment; local involved field radiotherapy for limited stage disease is not considered as a previous line.
    • Note: for SMZL, splenectomy is considered as 1 line; for ENMZL, Helicobacter pylori eradication is not considered as a previous line.
    • MCL: following at least 2 prior lines of therapy including at least 1 immunochemotherapy and 1 BTK inhibitor;
    • 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;
    • cHL: following at least 2 prior systemic lines of therapy and previously exposed to brentuximab vedotin and anti-PD1;
    • All other subtypes: following at least 2 prior lines of therapy;
    • Subjects previously treated with CAR-T therapy can be enrolled (irrespective of the indication).
  • Subjects must not be eligible for any other approved treatment for their underlying lymphoma as assessed by the Investigator.
  • 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.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Must have the following laboratory values:
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L or ≥ 1.0 x 10^9 /L in case of documented bone marrow involvement (> 50% or tumor cells), without growth factor support for 7 days (14 days if pegfilgrastim);
    • Hemoglobin (Hb) ≥ 8 g/dL;
    • Platelets (Plt) ≥ 75 x 10^9 /L or ≥ 50 x 10^9 /L in case of documented bone marrow involvement (> 50% or tumor cells), without transfusion for 7 days;
    • Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN;
    • Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert’s syndrome, then ≤ 3.0 ULN;
    • Estimated serum creatinine clearance of ≥ 50 mL/min using the modification of diet in renal disease formula or directly determined from the 24-hour urine collection method.
  • All subjects must:
    • Have an understanding that the study drug could have a potential teratogenic risk;
    • Agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment;
    • Agree not to share study medication with another person;
    • Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
  • Females must agree to abstain from breastfeeding during study participation and for at least 28 days after CC-220 discontinuation and according to the approved rituximab or obinutuzumab product/prescribing information.
  • Females of childbearing potential (FCBP*) must:
    • Have 2 negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence** from heterosexual contact;
    • Either commit to true abstinence** from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220, for 12 months after the last dose of rituximab or 18 months following the last dose of obinutuzumab, whichever is longer.
  • Male subjects must:
    • Practice true abstinence2 (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days after the last dose of CC-220, rituximab or obinutuzumab, whichever is longer, even if he has undergone a successful vasectomy;
    • Must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of CC-220, rituximab or obinutuzumab, whichever is longer.
  • *A FCBP is a female who:
    • has achieved menarche at some point;
    • has not undergone a hysterectomy or bilateral oophorectomy; or
    • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • ** True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Any significant medical condition, active infection (including severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  • Any condition that confounds the ability to interpret data from the study.
  • Life expectancy ≤ 3 months.
  • Diagnosis of lymphoblastic lymphoma.

Eligibility last updated 8/12/21. 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

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

Rochester, Minn.

Mayo Clinic principal investigator

Grzegorz Nowakowski, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

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

International patient clinical studies questions