Smart 3: A Multi-Center Phase 2 Trial Of Golcadomide, Glofitamab And Polatuzumab Vedotin (G2P) For Patients With Newly Diagnosed Large B-Cell Lymphoma

Eligibility Criteria

Participants must meet the following criteria for study entry:

Age ≥18 years

Histologically diagnosed

* Diffuse large B-cell lymphoma, not otherwise specified (NOS) or

* High grade B-cell lymphoma (NOS or MYC and BCL2 rearrangements) o Transformed indolent lymphomas are eligible

Ann Arbor stage II bulky (maximum dimension ≥7.5cm), III or IV

International Prognostic Index score ≥2

Participants must have bi-dimensional measurable disease, as defined as radiographically apparent disease with the longest dimension of ≥1.5cm

Performance status ≤2 on the ECOG scale, or 3 if related to lymphoma

Participants must have adequate organ and marrow function as defined below:

* Absolute neutrophil count (ANC) ≥1.0 × 109 /L

* Platelet count ≥75 × 109 /L

* Hemoglobin ≥ 8 g/dL

* Total bilirubin ≤ 3 ULN, unless consistent with Gilbert's

* AST and ALT ≤ 5x upper limit of normal (ULN)

* Alkaline phosphatase \< 2.5 ULN

* Creatinine clearance \>30 ml/min calculated by modified Cockcroft-Gault formula or eGFR \> 30 ml/min/1.73m2

* Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion (except trace or physiological) as determined by an echocardiogram (ECHO) or MUGA, and no clinically significant electrocardiogram (ECG) findings

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 12 months 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 for golcadomide Pregnancy Prevention Plan for Subjects in Clinical trials

* Females must refrain from donating egg while on study and for at least 28 days after the last dose of golcadomide.

Females must agree to abstain from breastfeeding while taking golcadomide and for at least 28 days after the last dose of golcadomide

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114 and ARMM Checklist Appendix 14.6). This includes all female patients, between the onset of menses (as early as 8 years of age) and 50 years unless the Participant presents with an applicable exclusionary factor which may be one of the following:

* Postmenopausal (no menses in greater than or equal to 12 consecutive months)

* History of hysterectomy or bilateral salpingo-oophorectomy

* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy)

* History of bilateral tubal ligation or another surgical sterilization procedure

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

* a negative serum or urine pregnancy test at Screening (within 10-14 days prior to Cycle 1 Day 1) of study treatment

* a negative serum or urine pregnancy test (Investigator's discretion) within 24 hours prior to Cycle 1 Day 1 of study treatment

* 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 28 days after the last dose of golcadomide, 2 months after the last dose of glofitamab, 9 months after the last dose of polatuzumab and for 18 months after the last dose of obinutuzumab or 3 months after the last dose of tocilizumab (if applicable), whichever is longer. Contraception requirements are detailed in

Male subjects must:

* Participants must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of \< 1% per year from screening until at least 28 days after the last dose of golcadomide, 3 months after pre-treatment with obinutuzumab, 2 months after the last dose of glofitamab, 6 months after the last dose of polatuzumab, or 2 months after the last dose of tocilizumab (if applicable), whichever is longer

), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study

* 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 golcadomide 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 Participant 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 Participant 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 decisionmaking 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 12 consecutive months

Participants must be willing and able to comply with the protocol treatment and procedures

Ability to understand and the willingness to sign a written informed consent document

Smart 3: A Multi-Center Phase 2 Trial Of Golcadomide, Glofitamab And Polatuzumab Vedotin (G2P) For Patients With Newly Diagnosed Large B-Cell Lymphoma

What this study is about

Smart 3: A Multi-Center Phase 2 Trial Of Golcadomide, Glofitamab And Polatuzumab Vedotin (G2P) For Patients With Newly Diagnosed Large B-Cell Lymphoma

What this study is about