Phase 2 Trial of Obinutuzumab and CC-99282 for Patients With Previously Untreated High Tumor Burden Follicular Lymphoma

Inclusion Criteria

• •Patients must meet the following criteria for study entry:
• •Histologically diagnosed follicular lymphoma grade 1-3a
• •Have no prior systemic treatment for lymphoma
• •Stage II, III or IV disease
• •Age ≥18 years
• •Performance status ≤2 on the ECOG scale
• •High-tumor burden disease based on GELF criteria36
• •A nodal or extranodal (except spleen) mass \> 7 cm in its greater diameter
• •At least 3 nodal or extranodal sites ≥ 3 cm in diameter
• •Presence of at least one B symptom
• •Fever (\>38 ℃), night sweats, weight loss \> 10% in the past 6 months
• •Symptomatic splenomegaly (or size \>13cm)
• •Impending organ compression or involvement (ureteral, orbital, gastrointestinal)
• •Any of the following cytopenias due to bone marrow involvement of lymphoma
• •Hemoglobin ≤ 10 g/dL
• •Platelets ≤ 100 x 109/L
• •Absolute neutrophil count (ANC) \< 1.5x109/L
• •Pleural effusion or ascites
• •Bi-dimensionally measurable disease, with at least one nodal lesion ≥ 1.5 cm or one extra-nodal lesion \> 1 cm in longest diameter by CT, PET/CT, and/or MRI
• •Bulky disease is defined as \> 10 cm in its greater diameter
• •Patients must have adequate organ and marrow function as defined below:
• •Total bilirubin ≤ 1.5 ULN, unless consistent with Gilbert's (ratio between total and direct bilirubin \> 5)
• •AST and ALT ≤ 3x upper limit of normal (ULN)
• •Alkaline phosphatase \< 2.5 ULN
• •Creatinine clearance \>50 ml/min calculated by modified Cockcroft-Gault formula
• •Blood counts below if without bone marrow lymphoma involvement
• •Hemoglobin ≥ 8 g/dL
• •Platelets ≥ 75 x 109/L
• •Absolute neutrophil count (ANC) ≥ 1.5x109/L
• •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 (see Appendix 14.1) for CC-99282 Pregnancy Prevention Plan for Subjects in Clinical trials.
• •Females must agree to abstain from breastfeeding while taking CC-99282 and for at least 6 months and 2 weeks after the last dose of CC-99282
• •Females of childbearing potential (FCBP§) must:
• •Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. 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 IP, during the study treatment (including dose interruptions), and for 6 months and 2 weeks for women and 3 months and 2 weeks for men after the last dose of CC-99282 and for 12 months after the last dose of obinutuzumab, whichever is longer. Contraception requirements are detailed in Appendix 14.1.
• •Male subjects must:
• •Practice true abstinence\* (which must be reviewed on a monthly basis and source documented) or agree to use a condom (Appendix 14.1) 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 3 months and 2 weeks after the last dose of CC-99282 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 3 months and 2 weeks after the last dose of CC-99282 or obinutuzumab, whichever is longer.
• •Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.
• •The investigator is responsible for: ensuring that the patient understands the potential risks and benefits of participating in the study; ensuring that informed consent is given by each patient, this includes obtaining the appropriate signatures and dates on the informed consent document prior to the performance of any study procedures and prior to the administration of study treatment; answering any questions the patient may have throughout the study and sharing in a timely manner any new information that may be relevant to the patient's willingness to continue his or her participant in the trial. Subjects will undergo a brief physical exam including a brief exam to determine cognitive review. No one without capacity to personally consent will be enrolled. Patients have medical decision-making capacity if they can demonstrate understanding of the situation, appreciation of the consequences of their decision, and reasoning in their thought process, and if they can communicate their wishes.
• •A determination of lack of decision-making capacity shall be made after an appropriate medical evaluation that concludes there is little or no likelihood that the participant will regain decision-making capacity in a reasonable period of time.
• •§A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, 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. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.