Rituxan + Bendamustine + PCI-32765 for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kami Maddocks

Must not be taking: QTc prolonging drugs

Disqualifiers: Cardiovascular 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: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of a new combination treatment for individuals with recurrent non-Hodgkin lymphoma (NHL). The treatment combines three components: PCI-32765, which may inhibit cancer cell growth; rituximab, which targets and kills cancer cells; and bendamustine, a chemotherapy drug that can kill or stop cancer cells from dividing. Individuals with specific types of NHL that have not responded to previous treatments might be suitable candidates. Those with a type of B-cell NHL unresponsive to at least one prior treatment might consider participating. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

The trial requires that you stop any immunotherapy, chemotherapy, radiotherapy, or experimental therapy at least 3 weeks before starting the study drug. Additionally, medications that prolong the QTc interval or may cause Torsades de Pointes must be stopped 7 days before and during the trial. Corticosteroids for disease-related symptoms are allowed but need a 1-week break before starting the study drug.

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

Research has shown that combining PCI-32765 with rituximab and bendamustine is generally well-tolerated. In one study, adding ibrutinib (another name for PCI-32765) to bendamustine and rituximab proved safe for patients with certain types of lymphoma. Most patients experienced only mild to moderate side effects, such as tiredness, low blood cell counts, and nausea.

Other studies using acalabrutinib, a drug similar to PCI-32765, also demonstrated safety when combined with bendamustine and rituximab. This suggests that the treatment combination might be safe for many patients. However, as this is still in an early phase of testing, researchers continue to study all possible side effects. Always consult a doctor about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Rituximab, Bendamustine, and PCI-32765 for treating lymphoma because it introduces a unique mechanism of action. Unlike traditional treatments that primarily rely on chemotherapy alone, this approach incorporates PCI-32765, a Bruton's tyrosine kinase (BTK) inhibitor, which targets specific pathways in cancer cells to prevent their growth and survival. This targeted action, combined with the immune system-boosting effects of Rituximab and the cancer-fighting power of Bendamustine, offers a potentially more effective and less toxic treatment option. This combination may provide benefits in cases where conventional treatments have limited success, offering hope for better outcomes in lymphoma management.

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

This trial will evaluate the combination of bendamustine, PCI-32765, and rituximab for treating certain types of lymphoma. Studies have shown that these treatments can be effective together. PCI-32765, a BTK inhibitor, blocks proteins that cancer cells need to grow. Patients treated with similar BTK inhibitors, along with bendamustine and rituximab, have experienced positive outcomes. Bendamustine, a chemotherapy drug, stops cancer cells from dividing, while rituximab, a special protein, helps the immune system find and destroy cancer cells. Together, these treatments have shown promise in slowing or reducing cancer growth in some research studies. ^{2 4 5 6 7}

Who Is on the Research Team?

Kami Maddocks, MD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for adults with certain types of B-cell non-Hodgkin lymphoma that have come back after treatment. They must weigh at least 40 kg, be fairly active (ECOG <=2), and agree to use birth control if they can have children. People who've had other cancers recently, serious illnesses, or major surgery aren't eligible. Also excluded are those with HIV/HBV/HCV infections, severe heart disease, or poor kidney/liver/blood function.

Inclusion Criteria

My body weight is at least 40 kg.

Agreement to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children

Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria

I have had cancer before, but I've been cancer-free for at least 2 years, or it won't shorten my life expectancy.

I don't have any severe illnesses that could affect my safety or the study's results.

I have experienced significant side effects from cancer treatment, excluding hair loss.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BTK inhibitor PCI-32765 orally once daily on days 1-28, rituximab intravenously on day 1, and bendamustine hydrochloride intravenously on days 1-2. Treatment repeats every 28 days for up to 6 courses.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 4 months for up to 2 years.

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine Hydrochloride
• PCI-32765
• Rituximab

Trial Overview The trial tests a combination of treatments: the BTK inhibitor PCI-32765 with rituximab and bendamustine hydrochloride in patients whose lymphoma has returned. It aims to find the safest dose that works best by blocking cancer cell growth enzymes and attacking cancer cells directly.

How Is the Trial Designed?

Group I: Treatment (enzyme inhibitor, chemo, monoclonal antibody) Experimental Treatment 6 Interventions

Patients receive BTK inhibitor PCI-32765 PO QD on days 1-28. Patients also receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue receiving BTK inhibitor PCI-32765 PO in the absence of disease progression or unacceptable toxicity.

Bendamustine Hydrochloride is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Approved in European Union as Levact for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)
• Multiple myeloma

Approved in Japan as Ribomustin for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Who Is Running the Clinical Trial?

Kami Maddocks

Lead Sponsor

Trials

4

Recruited

220+

Kami Maddocks, MD

Lead Sponsor

Trials

3

Recruited

220+

Pharmacyclics LLC.

Industry 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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01479842?cond=%22Mantle%20Cell%20Lymphoma%22&intr=%22Enzyme%20Inhibitors%22&viewType=Table&rank=1

Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or ... A general description of the clinical trial arm. It identifies the role of the intervention that participants receive. Types of arms include experimental arm, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00166

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or ... Retrospective data suggested that outcomes are poor in subsequent lines of therapy post-cBTKi, and definitive data are needed to help guide ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873691/

Safety and efficacy of acalabrutinib plus bendamustine and ... This multicenter, open-label, phase Ib study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naï ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2201817

Ibrutinib plus Bendamustine and Rituximab in Untreated ... Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01776840

NCT01776840 | A Study of the Bruton's Tyrosine Kinase ... The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab in patients 65 years of age ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01479842

Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, ... This phase I trial studies the side effects and best dose of BTK inhibitor PCI-32765 when given together with rituximab and bendamustine hydrochloride

7. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... A phase Ib trial demonstrated that acalabrutinib with bendamustine-rituximab produced durable responses with a tolerable safety profile in ...