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

Last updated: October 9, 2024
Sponsor: Nathan Denlinger
Overall Status: Active - Recruiting

Phase

1

Condition

Lymphoma, B-cell

Follicular Lymphoma

Lymphoma

Treatment

Biospecimen Collection

Positron Emission Tomography

Rituximab

Clinical Study ID

NCT06209619
OSU-23214
NCI-2023-10172
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Written informed consent obtained to participate in the study and Health InsurancePortability and Accountability Act (HIPAA) authorization for release of personalhealth information

  • Age ≥ 18 years at the time of consent

  • Diagnosis of B-cell Non-Hodgkin's lymphoma including either large B-cell lymphoma orfollicular lymphoma. Large B-cell subtypes include but are not limited to diffuselarge B-cell lymphoma, high grade B-cell lymphoma (except Burkitt's Lymphoma),primary mediastinal B-cell lymphoma, and diffuse large B cell lymphoma transformedfrom indolent lymphomas

  • Eastern Cooperative Oncology Group (ECOG) Score = 0-2

  • Prior receipt of standard of care CD19 directed CAR-T cell therapy includingaxicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel

  • Pre-CART imaging with PET within 60 days of infusion of CD19.CAR-T. If patient'sreceive bridging therapy, PET evaluation post bridging therapy is encouraged as partof institutional guidelines, but not mandated for inclusion

  • Evidence of objective response on PET/CT at 30 days post CD19.CAR-T infusion (+15/-5days) compared to baseline pre-CART PET imaging. Objective response in this trial isdefined by reduced fludeoxyglucose F-18 (FDG) uptake or reduction in mass size andincludes mixed response

  • Evidence of sub-optimal response to CD19.CAR-T as defined in this trial by DeauvilleScore ≥ 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 toinitiating study treatment)

  • Hematological lab values should be without the use of growth factors ortransfusion support

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Hemoglobin ≥ 8 x 10^9/L (obtained within 14 days prior to initiating studytreatment)

  • Hematological lab values should be without the use of growth factors ortransfusion support

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Platelets ≥ 50 x 10^9/L (obtained within 14 days prior to initiating studytreatment)

  • Hematological lab values should be without the use of growth factors ortransfusion support

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Estimated glomerular filtration rate (eGFR) (based on chronic kidneydisease-epidemiology collaboration [CKD-EPI] * patient's body surface area [BSA] [DuBois method]/1.73m^2) ≥ 45 ml/min (obtained within 14 days prior to initiating studytreatment)

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome maybe enrolled despite a total bilirubin level > 2.0 mg/dL if their conjugatedbilirubin is < 2.0 × ULN) (obtained within 14 days prior to initiating studytreatment)

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Aspartate aminotransferase (AST) ≤ 3.0 × ULN (obtained within 14 days prior toinitiating study treatment)

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Alanine aminotransferase (ALT) ≤ 3.0 × ULN (obtained within 14 days prior toinitiating study treatment)

  • Note: Changes in laboratory parameters during the study should not beconsidered adverse events unless they meet criteria for dose modification(s) ofstudy medication outlined by the protocol and/or worsen from baseline duringtherapy

  • Patients must be able to provide adequate tissue samples for minimal residualdisease (MRD) analysis for identification (ID) of baseline tumor deoxyribonucleicacid (DNA). 2 forms of tissue will be acceptable: optional baseline biopsy tissuepost CART and prior to initiation of CC-99282, or archival tumor tissue (ex.formalin-fixed paraffin embedded [FFPE] tumor blocks) from a biopsy containinglymphoma 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 3days prior to enrollment. Pregnancy tests must be medically supervised with aminimum sensitivity of 25mIU/ml. NOTE: a female of childbearing potential is afemale who: 1) has achieved menarche at some point, 2) has not undergone ahysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) forat least 24 consecutive months, i.e. has had menses at any time in the preceding 24consecutive months. Documentation of postmenopausal status must be provided. Furtherinformation on pregnancy testing and the definition of a female of childbearingpotential located in the CC-99282 pregnancy prevention plan document

  • Females of childbearing potential are required to use 2 forms of effective methodsof contraception or to agree to practice complete abstinence from the time ofinformed consent, without interruption, at least 28 days before starting CC-99282,throughout the entire duration of CC-99282, during dose interruptions and for atleast 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 oneadditional effective (barrier) method. Further information on acceptable methods islocated in the CC-99282 pregnancy prevention plan document

  • Male subjects with female partners must practice complete abstinence or agree to usea condom during sexual contact with a pregnant female or a female of child bearingpotential while taking CC-99282, during dose interruptions and for at least 3 monthsand 2 weeks following the last dose of CC-99282, even if he has undergone asuccessful vasectomy. Additional information regarding prevention of pregnancy as itpertains to male subjects is contained within the CC-99282 pregnancy prevention plandocument

  • Subjects with prior or concurrent malignancy whose natural history or treatment doesnot have the potential to interfere with the safety or efficacy assessment of theexperimental regimen are eligible for the trial

  • Subject is willing and able to comply with study procedures based on the judgementof the investigator or protocol designee

Exclusion

Exclusion Criteria:

  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use whilethe mother is being treated on study and lactating females must agree to notbreastfeed while taking study drugs)

  • Uncontrolled concomitant illness including, but not limited to, symptomaticcongestive 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 compensatedhypertension (Systolic blood pressure >= 180mmHg or diastolic blood pressure >= 120mmHg)

  • Receipt of CD19.CAR-T for any indication other than that stated within theinclusions criteria

  • Concomitant use of strong CYP3A inhibitors and inducers. Examples include (but arenot limited to):

  • CYP3A inhibitors: atazanavir, clarithromycin, indinavir, itraconazole,ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin.

  • CYP3A inducers: carbamazepine, phenytoin, and rifampin. Patients that are ableto come off moderate CYP3A inhibitors/inducers will require a washout period ofat least 14 days or 5 half-lives, whichever is shorter, prior to the initiationof 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

Study Design

Total Participants: 18
Treatment Group(s): 6
Primary Treatment: Biospecimen Collection
Phase: 1
Study Start date:
January 29, 2024
Estimated Completion Date:
December 31, 2025

Study Description

PRIMARY OBJECTIVE:

I. To determine the safety profile and maximum tolerated dose (MTD) of early, risk adapted golcadomide (CC-99282)/rituximab for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) post-commercial CD19.CAR-T infusion.

SECONDARY OBJECTIVES:

I. To perform a preliminary efficacy analysis of CC-99282 and rituxan early post CD19.CAR-T defined as the progression free survival (PFS) rate at day+150 post initiation of CC-99282.

II. To describe disease response rates in patients with active disease who are treated with CC-99282 + rituximab.

III. To estimate PFS in subjects treated with CC-99282 + rituximab. IV. To estimate the overall survival (OS) in subjects treated with CC-99282 + rituximab.

EXPLORATORY OBJECTIVES:

I. To describe CD19.CAR-T cell expansion and persistence following treatment with CC-99282/rituximab.

II. To evaluate CC-99282/rituximab's effect on CAR T-cells and other immune cell subsets composition and how this effects clinical outcomes.

III. To evaluate CC-99282/rituximab's effect on CAR T-cell and other immune cell subset function and how this effects clinical outcomes.

IV. To evaluate CC-99282/rituximab's effect on the tumor microenvironment (TME) and how this effects clinical outcomes.

OUTLINE: This is a dose-escalation study of CC-99282 in combination with fixed-dose rituximab.

Patients receive rituximab intravenously (IV) on day 1 of each cycle and CC-99282 orally (PO) once daily (QD) on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 24 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial. Patients may undergo biopsy at screening.

After completion of study treatment, patients are followed up at days 240, 365, 455, 547, 637, and 730.

Connect with a study center

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio 43210
    United States

    Active - Recruiting

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