CC-486 + Lenalidomide + Obinutuzumab for Non-Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph Tuscano

Must be taking: Aspirin

Must not be taking: Efavirenz, Stavudine, Zidovudine

Disqualifiers: Active hepatitis B or C, Autoimmune disease, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 cycles (approximately 48 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of three treatments—CC-486 (an oral drug), lenalidomide (Revlimid), and obinutuzumab (Gazyva)—for individuals with certain types of B-cell lymphoma, a cancer affecting the immune system's cells. The trial targets patients whose cancer has returned or hasn't responded to previous treatments. The goal is to determine if this combination can enhance cancer response and reduce side effects. Individuals diagnosed with specific types of B-cell lymphoma, such as follicular lymphoma or mantle cell lymphoma, who have undergone prior treatment, might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications to join the trial?

The trial requires that all previous cancer therapy, including radiation, hormonal therapy, and surgery, must be stopped at least 4 weeks before starting the study. However, it does not specify if you need to stop other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is examining the safety of combining CC-486, lenalidomide, and obinutuzumab for patients with certain types of lymphoma. Early results indicate that patients can tolerate this treatment mix, though the study remains in its initial stages. The main side effects reported include tiredness and low blood counts, common with treatments affecting the immune system.

CC-486, also known as oral azacitidine, is a chemotherapy drug that may cause side effects like nausea and vomiting, but these are usually manageable. Lenalidomide, already approved for other conditions, can sometimes lead to tiredness or low blood counts. Obinutuzumab, an antibody therapy, may cause infusion reactions such as fever or chills, but these are generally mild.

While these treatments have been studied both separately and together, ongoing research aims to ensure their safety and effectiveness when used in combination. Always consult a doctor to understand what participating in such a trial might mean. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for Non-Hodgkin's Lymphoma because it brings together three promising therapies: CC-486, Lenalidomide, and Obinutuzumab. Unlike standard treatments, which often focus on chemotherapy, this approach integrates a novel oral form of azacitidine (CC-486) that modulates the immune system and a monoclonal antibody (Obinutuzumab) that targets and destroys cancerous cells. Additionally, Lenalidomide boosts the immune response to help fight the cancer. This combination aims to enhance effectiveness while potentially reducing the side effects associated with traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research has shown that CC-486 may help treat certain types of lymphoma. In earlier studies, 94.9% of patients responded well, and 88.1% experienced complete cancer remission. Lenalidomide has also proven effective for non-Hodgkin lymphoma, with 97% of patients responding and 79% achieving complete remission in one study. Obinutuzumab lowered the risk of disease progression or death by 32% compared to another treatment, with a 93.8% response rate in non-Hodgkin lymphoma patients. This trial tests these treatments together to determine if they can more effectively combat B-cell lymphoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Joseph M. Tuscano

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for patients with CD20 positive B-cell lymphoma that's returned or hasn't responded to treatment. Participants must have had prior treatments, be able to consent, follow the study schedule, and swallow pills. They should not have other serious medical conditions or be on conflicting medications.

Inclusion Criteria

Patients must be willing to be followed at a minimum of approximately every 3 months by physician expert in HIV disease management

All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program, and be willing and able to comply with the requirements of the REMS program

I can take daily aspirin or a substitute if I'm allergic.

Exclusion Criteria

My lymphoma has spread to my brain or spinal cord.

I am not using any other cancer treatments.

I have hepatitis B or C but am on treatment with no liver damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive azacitidine, obinutuzumab, and lenalidomide in cycles. Initial cycle lasts 35 days, followed by 28-day cycles for up to 12 cycles.

Up to 12 cycles (approximately 48 weeks)

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• CC-486
• Lenalidomide
• Obinutuzumab

Trial Overview The trial tests CC-486 combined with lenalidomide and obinutuzumab for recurrent/refractory B-cell lymphoma. It explores how well this combination works and its safety profile in improving patient outcomes while minimizing side effects.

How Is the Trial Designed?

Group I: Treatment (lenalidomide, oral azacitidine, obinutuzumab) Experimental Treatment 3 Interventions

Patients receive azacitidine PO QD on days 1-21, obinutuzumab IV over on days 8, 15, 22, and 29, and lenalidomide PO QD on days 8-28 of cycle 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Patients then receive azacitidine PO QD on days 1-21, obinutuzumab IV over on day 1, and lenalidomide PO QD on days 1-21. Cycles repeats every 28 days in the absence of disease progression, unacceptable toxicity, or until stem cell transplant. Patients who achieve SD, PR, or CR do not proceed to stem cell transplant may continue treatment for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Joseph Tuscano

Lead Sponsor

Trials

8

Recruited

180+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119807097

A Phase I, Open Label, Multicenter Trial of Oral Azacitidine ... CC-486 dose reduction occurred in 9 (27%) pts due to adverse events (AEs). Treatment with CC-486 (150 mg) was discontinued in 1 patient due to febrile ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10356559/

Multicenter phase 2 study of oral azacitidine (CC-486) plus ... With the exception of anaplastic large cell lymphoma (ALCL), CHOP typically delivers a overall response rate (ORR) of 60% to 80%, complete response (CR) of 30% ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/7265/Oral-Azacitidine-Plus-CHOP-Shows-Efficacy-in

Oral Azacitidine Plus CHOP Shows Efficacy in Treatment ... The two-year progression-free survival rate was 65.8% (95% CI 43.4-88.1) for all 20 patients and 69.2% (95% CI 46.7-91.7) for patients with PTCL ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9211445/

Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in ... The overall response rate was 94.9%, with 52 patients (88.1%) achieving complete responses. With a median follow-up of 28.9 months, estimated 1- and 2-year ...

5. ash.confex.com ash.confex.com/ash/2020/webprogram/Paper136023.html

40 Multi-Center Phase II Study of Oral Azacitidine (CC-486) ... To date, the preliminary end-of-treatment (EOT, n=17) CR was 76.5% (90%CI of 53.9%-91.5%) for all evaluable patients and was 86.7% for 15 PTCL- ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6317/528131/A-Phase-I-Trial-of-CC-486-Lenalidomide

A Phase I Trial of CC-486, Lenalidomide, Obinutuzumab in ... In this single-center phase I study, we evaluated the safety and efficacy of the triplet combination that includes CC-486, lenalidomide, and obituzumab in R/R ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04578600

Study Details | CC-486, Lenalidomide, and Obinutuzumab ... This phase I/Ib trial investigates the side effects of CC-486 and how well it works in combination with lenalidomide and obinutuzumab in treating patients ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124091444

A Phase I Trial of CC-486, Lenalidomide, Obinutuzumab in ... In this single-center phase I study, we evaluated the safety and efficacy of the triplet combination that includes CC-486, lenalidomide, and obituzumab in R/R ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39731545/

A phase I trial of CC-486, lenalidomide, obinutuzumab in ... A phase I trial of CC-486, lenalidomide, obinutuzumab in relapsed/refractory indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2025 May;66(5):961-964. doi ...