CC-99282 + Rituximab Early Post CART for Non-Hodgkin's Lymphoma

Launched by NATHAN DENLINGER · Jan 8, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment combination of CC-99282 and rituximab for patients with certain types of B-cell non-Hodgkin lymphoma who did not respond well to a previous CAR T-cell therapy. The goal is to see if this combination is safe, what side effects might occur, and the best dose to use. CC-99282 is an immunotherapy that may help boost the body's immune response against cancer, while rituximab helps the immune system target cancer cells that have a specific protein called CD20 on their surface.

To be eligible for this trial, participants must be at least 18 years old and have been diagnosed with specific types of B-cell non-Hodgkin lymphoma. They should have already received a standard CAR T-cell therapy but experienced a less-than-ideal response soon after. Participants will need to provide consent, undergo various health tests, and may need to provide tissue samples for analysis. Those who join the study can expect close monitoring for any side effects and to receive the new treatment in hopes of improving their cancer response. It's important for potential participants to discuss with their doctor if they meet the eligibility criteria and to understand the commitment involved in joining the trial.

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ALL

Eligibility criteria

• Inclusion Criteria:
• • Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• • Age ≥ 18 years at the time of consent
• • Diagnosis of B-cell Non-Hodgkin's lymphoma including either large B-cell lymphoma or follicular lymphoma. Large B-cell subtypes include but are not limited to diffuse large B-cell lymphoma, high grade B-cell lymphoma (except Burkitt's Lymphoma), primary mediastinal B-cell lymphoma, and diffuse large B cell lymphoma transformed from indolent lymphomas
• • Eastern Cooperative Oncology Group (ECOG) Score = 0-2
• • Prior receipt of standard of care CD19 directed CAR-T cell therapy including axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel
• • Pre-CART imaging with PET within 60 days of infusion of CD19.CAR-T. If patient's receive bridging therapy, PET evaluation post bridging therapy is encouraged as part of institutional guidelines, but not mandated for inclusion
• • Evidence of objective response on PET/CT at 30 days post CD19.CAR-T infusion (+15/-5 days) compared to baseline pre-CART PET imaging. Objective response in this trial is defined by reduced fludeoxyglucose F-18 (FDG) uptake or reduction in mass size and includes mixed response
• • Evidence of sub-optimal response to CD19.CAR-T as defined in this trial by Deauville Score ≥ 3 on PET/CT at 30 days post CART infusion (+15/-5 days)
• • Absolute neutrophil count ≥ 7.5 x 10\^8/L (obtained within 14 days prior to initiating study treatment)
• • Hematological lab values should be without the use of growth factors or transfusion support
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Hemoglobin ≥ 8 x 10\^9/L (obtained within 14 days prior to initiating study treatment)
• • Hematological lab values should be without the use of growth factors or transfusion support
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Platelets ≥ 50 x 10\^9/L (obtained within 14 days prior to initiating study treatment)
• • Hematological lab values should be without the use of growth factors or transfusion support
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Estimated glomerular filtration rate (eGFR) (based on chronic kidney disease-epidemiology collaboration \[CKD-EPI\] \* patient's body surface area \[BSA\] \[Du Bois method\]/1.73m\^2) ≥ 45 ml/min (obtained within 14 days prior to initiating study treatment)
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 2.0 mg/dL if their conjugated bilirubin is \< 2.0 × ULN) (obtained within 14 days prior to initiating study treatment)
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Aspartate aminotransferase (AST) ≤ 3.0 × ULN (obtained within 14 days prior to initiating study treatment)
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Alanine aminotransferase (ALT) ≤ 3.0 × ULN (obtained within 14 days prior to initiating study treatment)
• • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• • Patients must be able to provide adequate tissue samples for minimal residual disease (MRD) analysis for identification (ID) of baseline tumor deoxyribonucleic acid (DNA). 2 forms of tissue will be acceptable: optional baseline biopsy tissue post CART and prior to initiation of CC-99282, or archival tumor tissue (ex. formalin-fixed paraffin embedded \[FFPE\] tumor blocks) from a biopsy containing lymphoma prior to CD19.CART
• • Fridericia's formula-corrected QT interval (QTcF) \< 470 ms
• • Patients must be able to swallow/absorb capsules
• • Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment. Pregnancy tests must be medically supervised with a minimum sensitivity of 25mIU/ml. NOTE: a female of childbearing potential 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, i.e. has had menses at any time in the preceding 24 consecutive months. Documentation of postmenopausal status must be provided. Further information on pregnancy testing and the definition of a female of childbearing potential located in the CC-99282 pregnancy prevention plan document
• • Females of childbearing potential are required to use 2 forms of effective methods of contraception or to agree to practice complete abstinence from the time of informed consent, without interruption, at least 28 days before starting CC-99282, throughout the entire duration of CC-99282, during dose interruptions and for at least 6 months and 2 weeks after the last dose of golcadomide (BMS-986369)/CC-99282. The two contraception methods can be comprised one highly effective method and one additional effective (barrier) method. Further information on acceptable methods is located in the CC-99282 pregnancy prevention plan document
• • Male subjects with female partners must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of child bearing potential while taking CC-99282, during dose interruptions and for at least 3 months and 2 weeks following the last dose of CC-99282, even if he has undergone a successful vasectomy. Additional information regarding prevention of pregnancy as it pertains to male subjects is contained within the CC-99282 pregnancy prevention plan document
• • Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial
• • Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• Exclusion Criteria:
• • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drugs)
• • Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non compensated hypertension (Systolic blood pressure \>= 180mmHg or diastolic blood pressure \>= 120mmHg)
• • Receipt of CD19.CAR-T for any indication other than that stated within the inclusions criteria
• * Concomitant use of strong CYP3A inhibitors and inducers. Examples include (but are not limited to):
• • CYP3A inhibitors: atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin.
• • CYP3A inducers: carbamazepine, phenytoin, and rifampin. Patients that are able to come off moderate CYP3A inhibitors/inducers will require a washout period of at least 14 days or 5 half-lives, whichever is shorter, prior to the initiation of study treatment
• • Patients who are actively receiving or have received other investigational agents, including herbal supplements, within 2 weeks or 5 half-lives of enrollment