What is the mechanism of action of this treatment?

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies and small molecule inhibitors. Monoclonal antibodies, such as Obinutuzumab, target specific proteins like CD20 on the surface of B-cells, leading to the destruction of these malignant cells through immune-mediated mechanisms. Small molecule inhibitors target specific pathways essential for cancer cell survival and proliferation. These targeted therapies are significant for NHL patients as they offer a more precise approach to treatment, potentially reducing side effects and improving efficacy compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, particularly those involving monoclonal antibodies targeting CD20 like Obinutuzumab, often have side effects such as infusion-related reactions, neutropenia, and thrombocytopenia. For instance, Obinutuzumab is associated with severe infusion-related reactions (21%), neutropenia (34%), and thrombocytopenia (12%). When combined with chemotherapy agents like chlorambucil, these treatments can also lead to increased rates of severe adverse events, including higher incidences of infections and other hematologic toxicities.

What prior FDA approvals exist?

The FDA has approved several monoclonal antibodies targeting CD20 for the treatment of Non-Hodgkin's Lymphoma (NHL). Rituximab, a chimeric anti-CD20 monoclonal antibody, was one of the first to gain approval and has been used extensively in combination with chemotherapy regimens such as fludarabine, cyclophosphamide, and rituximab (FCR). More recently, Obinutuzumab, a novel anti-CD20 monoclonal antibody with glycoengineered properties, received FDA approval for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL). Obinutuzumab has also been studied in combination with other agents like bendamustine for rituximab-refractory indolent NHL. These approvals highlight the evolving landscape of immunotherapy in NHL, with a focus on enhancing efficacy through combination therapies.

What other types of research exist?

Promising alternatives to CC-99282 in combination with Obinutuzumab for Non-Hodgkin's Lymphoma patients include: 1) Obinutuzumab plus Idasanutlin, which has shown superior efficacy in preclinical models by inducing direct cell death and antibody-dependent cellular cytotoxicity (ADCC). 2) Obinutuzumab plus Bendamustine, which has demonstrated significant clinical activity and overall survival benefit in patients with rituximab-refractory indolent NHL. 3) Obinutuzumab plus Venetoclax, which has shown superior efficacy and tolerability in patients with chronic lymphocytic leukemia (CLL) and coexisting conditions, and may be applicable to NHL patients.

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BCL-2 inhibitor

CC-99282 + Obinutuzumab for Chronic Lymphocytic Leukemia

Phase 1

Waitlist Available

Research Sponsored by Celgene

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Subject is ≥18 years of age

Must not have

Subject has received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to starting CC-99282.

Uncontrolled/active autoimmune hemolytic anemia or thrombocytopenia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 3 years

Awards & highlights

Summary

This trial tests a new drug (CC-99282) with an existing one (Obinutuzumab) in patients with a specific type of leukemia or lymphoma who haven't responded to other treatments. The goal is to see if the combination is safe and effective in fighting cancer.

Who is the study for?

Adults over 18 with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma who've had at least two prior treatments, including a BTK inhibitor. They must have measurable disease, adequate organ function, and no recent history of certain other cancers or treatments like CAR-T therapy.

What is being tested?

The trial is testing the safety and early effectiveness of CC-99282 combined with Obinutuzumab in patients whose CLL/SLL has come back or didn't respond to treatment. It's an early-phase study that gradually increases doses to find safe levels.

What are the potential side effects?

Potential side effects are not detailed here but may include reactions related to the immune system due to Obinutuzumab, as well as any risks associated with new drug CC-99282 which will be monitored closely during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am able to care for myself and perform daily activities.

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I am 18 years old or older.

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My condition did not improve after 2+ treatments, including a BTK inhibitor.

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My spleen is enlarged, measuring at least 14 cm long.

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My kidneys are functioning well.

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I am able to get out of my bed or chair and move around.

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My liver is enlarged, measuring at least 20 cm in length.

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I have been diagnosed with CLL/SLL and need treatment.

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I have CLL/SLL that needs treatment and measurable signs of the disease.

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My white blood cell count is within the required range without medication help.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had CAR-T or similar therapy less than 4 weeks ago.

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I do not have active autoimmune blood disorders.

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I have ongoing severe diarrhea or nutrient absorption issues not improved with treatment.

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My condition has progressed to Richter's Syndrome.

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I do not have another cancer that affects my life expectancy or requires treatment that would interfere with the study.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I have heart problems that affect my daily activities.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adverse Events (AEs)

Dose Limiting Toxicity (DLT)

Maximum tolerated dose (MTD)

Secondary study objectives

Complete response with incomplete marrow recovery (CRi)

Duration of response (DoR)

Nodular partial response (nPR)

+11 more

Side effects data

From 2023 Phase 1 & 2 trial • 62 Patients • NCT03310619

71%

White blood cell count decreased

65%

Neutrophil count decreased

59%

Anaemia

59%

Lymphocyte count decreased

53%

Platelet count decreased

41%

Cytokine release syndrome

29%

Neutropenia

29%

Decreased appetite

18%

Diarrhoea

18%

Vomiting

18%

Muscular weakness

18%

Dizziness

18%

Neurotoxicity

18%

Insomnia

18%

Pleural effusion

18%

Hypertension

12%

Hypoxia

12%

Pyrexia

12%

Febrile neutropenia

12%

Thrombocytopenia

12%

Tachycardia

12%

Conjunctival haemorrhage

12%

Fatigue

12%

Pain

12%

Contusion

12%

Hyperuricaemia

12%

Hypokalaemia

12%

Hypomagnesaemia

12%

Tremor

12%

Dyspnoea

12%

Pruritus

Blood creatinine increased

Hypercalcaemia

Atrial fibrillation

Extrasystoles

Appetite disorder

Enteritis

COVID-19

Pneumonia

Agraphia

Large intestine perforation

Hypofibrinogenaemia

Supraventricular extrasystoles

Ventricular tachycardia

Periorbital oedema

Visual impairment

Abdominal distension

Abdominal pain

Anal incontinence

Constipation

Dry mouth

Gastrointestinal disorder

Oedema

Oedema peripheral

Physical deconditioning

Jaundice

Ocular icterus

Conjunctivitis

Cytomegalovirus infection reactivation

Urinary tract infection

Fall

Alanine aminotransferase increased

Blood bilirubin increased

Dehydration

Hypocalcaemia

Hypophosphataemia

Arthralgia

Musculoskeletal chest pain

Amnesia

Peroneal nerve palsy

Anxiety

Confusional state

Urinary retention

Cough

Oropharyngeal pain

Night sweats

Seborrhoeic dermatitis

Deep vein thrombosis

Haematoma

Hypotension

100%

80%

60%

40%

20%

Study treatment Arm

Arm D: Cohort 1A JCAR017 Plus Ibrutinib (Pre- and Post-JCAR017 Infusion)

Arm F: Cohort 1A Cohort 1A and 1D JCAR017 Plus CC-99282 (Post-JCAR017 Infusion)

Arm A: Cohort 1A JCAR017 Plus Durvalumab (Post-JCAR017 Infusion)

Arm A: Cohort 1B JCAR017 Plus Durvalumab (Post-JCAR017 Infusion)

Arm B: Cohort 1A JCAR017 Plus CC-122 (Post-JCAR017 Infusion)

Arm C: Cohort 1A JCAR017 Plus CC-220 (Iberdomide) (Post-JCAR017 Infusion)

Arm E: Cohort 1C JCAR017 Plus Relatlimab and/or Nivolumab (Post-JCAR017 Infusion)

Arm F: Cohort 1D Cohort 1A and 1D JCAR017 Plus CC-99282 (Post-JCAR017 Infusion)

Trial Design

1Treatment groups

Experimental Treatment

Group I: CC-99282 + obinutuzumabExperimental Treatment2 Interventions

Escalating doses of CC-99282 administered orally once daily on intermittent schedules with obinutuzumab IV infusion 1000 mg up to 2 years in Part A. CC-99282 administered orally once daily at MTD or alternative tolerating dosing schedule with obinutuzumab IV infusion 1000 mg up to 2 years in Part B.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CC-99282

2020

Completed Phase 2

~80

Obinutuzumab

2014

Completed Phase 3

~3470

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies and small molecule inhibitors. Monoclonal antibodies, such as Obinutuzumab, target specific proteins like CD20 on the surface of B-cells, leading to the destruction of these malignant cells through immune-mediated mechanisms. Small molecule inhibitors target specific pathways essential for cancer cell survival and proliferation. These targeted therapies are significant for NHL patients as they offer a more precise approach to treatment, potentially reducing side effects and improving efficacy compared to traditional chemotherapy.

Oncologic, endocrine & metabolic emerging drugs in B-cell non-Hodgkin's lymphoma.Novel treatments in B cell non-Hodgkin's lymphomas.Ublituximab for the treatment of CD20 positive B-cell malignancies.