Ibrutinib + Rituximab for Follicular Lymphoma

No longer recruiting at 199 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharmacyclics LLC.

Disqualifiers: Transformed lymphoma, Prior treatment, CNS lymphoma, Cardiovascular disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding ibrutinib, a cancer drug, to rituximab can help people with follicular lymphoma live longer without disease progression, compared to rituximab alone. Follicular lymphoma is a blood cancer affecting a type of white blood cell. The study includes two groups: one receiving both ibrutinib and rituximab, and the other receiving a placebo with rituximab. It seeks participants who have been newly diagnosed with follicular lymphoma, have a confirmed diagnosis, and are experiencing symptoms that impact daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that patients generally tolerate the combination of ibrutinib and rituximab well. In past studies, most participants experienced only mild to moderate side effects, such as fatigue, mild nausea, and low blood cell counts. Serious side effects, like infections and bleeding, were less common.

Despite these risks, many patients have continued treatment without major issues. Evidence suggests that while side effects exist, they are manageable for most people. Anyone considering joining the trial should discuss these potential side effects with their doctor to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for follicular lymphoma?

Researchers are excited about the combination of ibrutinib and rituximab for follicular lymphoma because it offers a novel approach compared to standard treatments. While traditional therapies typically focus on targeting the cancer cells directly, ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that interferes with the signaling pathways crucial for the survival and proliferation of lymphoma cells. This mechanism of action is distinct from the usual chemotherapy or rituximab treatment alone. By combining ibrutinib with rituximab, there's potential for a more effective disruption of the cancer's growth, offering hope for improved outcomes in patients.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that using ibrutinib with rituximab may effectively treat follicular lymphoma. One study found that 82% of patients experienced a reduction or disappearance of their cancer with this combination. Additionally, 30% of patients showed no detectable signs of cancer after treatment. Another study found that this combination helped patients live longer without their cancer worsening. In this trial, one group of participants will receive ibrutinib and rituximab, while another group will receive a placebo with rituximab. These results suggest that adding ibrutinib to rituximab might be more effective than using rituximab alone. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 60 and older with untreated follicular lymphoma, who meet specific health criteria. They should have a certain level of physical fitness (ECOG score 0-2) and their liver and kidneys must work well. People with transformed lymphoma, brain or spinal cord lymphoma, serious heart conditions, or previous treatments for this cancer can't join.

Inclusion Criteria

My liver and kidney functions are within normal ranges.

My cancer can be measured by tests.

I am 70 or older, or I am 60-69 with one or more health conditions.

Exclusion Criteria

I have a serious heart condition that is currently causing symptoms.

I have received treatment for follicular lymphoma before.

My cancer affects my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib or placebo in combination with rituximab weekly for 4 weeks with maintenance

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for progression-free survival and other outcomes

2-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Placebo to match Ibrutinib
• Rituximab

Trial Overview The study tests if adding Ibrutinib to Rituximab therapy extends the time patients live without their cancer getting worse compared to using Rituximab alone. Participants will either receive Ibrutinib plus Rituximab or a placebo (inactive substance) plus Rituximab.

How Is the Trial Designed?

Group I: (Arm A) ibrutinib + rituximab Experimental Treatment 2 Interventions

Participants will receive 560mg of ibrutinib and rituximab 375mg/m\^2 weekly x4 with maintenance.

Group II: (Arm B) placebo + rituximab Placebo Group 2 Interventions

Participants will receive placebo and rituximab 375mg/m\^2 weekly x4 with maintenance.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Pharmacyclics LLC.

Lead Sponsor

Trials

114

Recruited

13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Published Research Related to This Trial

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

In a phase 1b/2 study involving 61 patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the combination of ibrutinib and durvalumab showed an overall response rate of 25%, with the highest response in non-GCB DLBCL patients (38%).

The treatment was generally well-tolerated, with common side effects including diarrhea, fatigue, and nausea, and a notable 20% of patients experienced immune-related adverse events, indicating that while the combination therapy is effective, it also carries additional risks compared to single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. Herrera, AF., Goy, A., Mehta, A., et al.[2021]

In a study of 838 patients with untreated non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL), the combination of ibrutinib and R-CHOP did not improve event-free survival (EFS) for the overall population, but showed significant benefits for patients under 60 years old, improving EFS, progression-free survival (PFS), and overall survival (OS).

For patients aged 60 and older, the combination treatment worsened EFS, PFS, and OS, increased serious adverse events, and reduced the number of patients able to complete the full R-CHOP regimen, indicating that age significantly influences the safety and efficacy of ibrutinib in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non-Germinal Center B-Cell Diffuse Large B-Cell Lymphoma. Younes, A., Sehn, LH., Johnson, P., et al.[2022]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

The combination of rituximab and ibrutinib in a 57-year-old patient with mantle cell lymphoma led to a severe disseminated enterovirus infection, highlighting the significant risk of immunodeficiency and severe immune-related side effects from this treatment regimen.

High-dose intravenous immunoglobulins were effective in clearing the virus and restoring organ function, suggesting that this treatment should be considered for patients experiencing severe enterovirus infections while on rituximab and ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report. Higer, M., Cana, D., Podlech, J., et al.[2021]

In a phase 2 study involving 80 adults with untreated follicular lymphoma, the combination of ibrutinib and rituximab showed a high overall response rate of 85% in the first treatment arm and 75% in the second arm, indicating strong efficacy.

The treatment was generally well-tolerated, with common side effects including fatigue, diarrhea, and nausea, while serious adverse events were rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. Fowler, NH., Nastoupil, L., De Vos, S., et al.[2021]

In the HELIOS trial involving 578 subjects, the combination of bendamustine/rituximab and ibrutinib (BR-I) resulted in significantly higher systemic exposure to rituximab compared to bendamustine/rituximab with placebo (BR), particularly in the initial treatment cycles.

The study found no significant safety differences between the BR-I and BR groups, suggesting that the enhanced efficacy of BR-I may be achieved without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial. Lavezzi, SM., de Jong, J., Neyens, M., et al.[2021]

In the phase 3 HELIOS trial involving 578 patients with previously treated chronic lymphocytic leukemia (CLL), the combination of ibrutinib and bendamustine-rituximab (BR) significantly improved progression-free survival (PFS) compared to placebo+BR, with a median PFS not reached for ibrutinib+BR versus 14.3 months for placebo+BR.

The treatment with ibrutinib+BR also resulted in a higher rate of minimal residual disease (MRD)-negative responses (26.3% vs. 6.2% for placebo+BR), indicating a deeper response to therapy, while the safety profile remained consistent with earlier reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Fraser, G., Cramer, P., Demirkan, F., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7317728/

The combination of ibrutinib and rituximab demonstrates ... The most common adverse events were fatigue, diarrhoea and nausea. Higher grade (Grade 3/4) haematological, haemorrhagic and cardiac events occurred ...

2. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35114

Safety and efficacy of ibrutinib in combination with rituximab ... In patients treated with lenalidomide and rituximab in the RELEVANCE trial, the ORR was 61% and CRR was 48%. CRR at 120 weeks was 48%. The 6- ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/235/531189/Ibrutinib-Rituximab-Is-Superior-to-Rituximab

Ibrutinib-Rituximab Is Superior to Rituximab-Chemotherapy in ... With a median follow up of 47.9 months, ENRICH is the first randomised trial to demonstrate a significant improvement in PFS for IR compared to ...

4. conference-correspondent.com conference-correspondent.com/highlights/ash/1105:ibrutinib-plus-rituximab-in-treatment-naive-patients-with-follicular-lymphoma-results-from-a-phase-2-study

Ibrutinib plus Rituximab in Treatment-Naive Patients with ... At a median follow-up of 13.8 months, patients with ibrutinib therapy achieved an investigator-assessed ORR of 82%, including a CR rate of 30% and partial ...

5. jhoponline.com jhoponline.com/articles/imbruvica-ibrutinib-plus-rituxan-rituximab-new-combination-approved-for-the-treatment-of-waldenstroem-s-macroglobulinemia

Imbruvica (Ibrutinib) plus Rituxan (Rituximab) New ... The efficacy of ibrutinib plus rituximab in treatment-naïve or in patients with previously treated Waldenström's macroglobulinemia was evaluated in the phase 3 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37985359/

Safety and efficacy of ibrutinib in combination with rituximab ... Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma: ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01974440

NCT01974440 | A Study of PCI-32765 (Ibrutinib) in ... The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered in combination with either bendamustine and rituximab ...

8. ashpublications.org ashpublications.org/bloodadvances/article/7/22/7141/497951/Phase-3-SELENE-study-ibrutinib-plus-BR-R-CHOP-in

Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in ... SELENE is a phase 3, placebo-controlled trial evaluating ibrutinib or placebo added to BR/R-CHOP for patients with R/R FL or MZL. The addition of ibrutinib ...