RECRUITING

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

Conditions

B-Cell Non-Hodgkin Lymphoma-Recurrent Diffuse Large B-Cell Lymphoma-Recurrent Follicular Lymphoma-Recurrent High Grade B-Cell Lymphoma-Recurrent Primary Mediastinal Large B-Cell Lymphoma-Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent B-Cell Non-Hodgkin Lymphoma-Refractory Diffuse Large B-Cell Lymphoma-Refractory Follicular Lymphoma-Refractory High Grade B-Cell Lymphoma-Refractory Primary Mediastinal Large B-Cell Lymphoma-Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Refractory

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial tests the safety, side effects and best dose of CC-99282 with rituximab for the treatment of patients who have received chimeric antigen receptor (CAR) T cell therapy for non-Hodgkins lymphoma and in whom have had a sub-optimal response early on to CAR T-cell therapy. Immunotherapy with CC-99282 may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving CC-99282 with rituximab may be a safe and effective treatment option for patients who have received CAR-T cell therapy for relapsed or refractory non-Hodgkin's lymphoma.

Official Title

Early, Risk Adapted CC-99282 + Rituximab Post CAR T-Cell Therapy for Non-Hodgkin's Lymphoma

Quick Facts

Study Start:2024-01-29

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06209619

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

The Ohio State Comprehensive Cancer Center

CONTACT

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Principal Investigator

Nathan Denlinger, DO, MS

PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Study Locations (Sites)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Collaborators and Investigators

Sponsor: Nathan Denlinger

Nathan Denlinger, DO, MS, PRINCIPAL_INVESTIGATOR, Ohio State University Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-29

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2024-01-29

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

B-Cell Non-Hodgkin Lymphoma-Recurrent
Diffuse Large B-Cell Lymphoma-Recurrent
Follicular Lymphoma-Recurrent
High Grade B-Cell Lymphoma-Recurrent
Primary Mediastinal Large B-Cell Lymphoma-Recurrent
Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent
B-Cell Non-Hodgkin Lymphoma-Refractory
Diffuse Large B-Cell Lymphoma-Refractory
Follicular Lymphoma-Refractory
High Grade B-Cell Lymphoma-Refractory
Primary Mediastinal Large B-Cell Lymphoma-Refractory
Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Refractory