Ibrutinib + Brentuximab Vedotin for Hodgkin's Lymphoma

No longer recruiting at 2 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Warfarin, Strong CYP3A4/5 inhibitors

Disqualifiers: Uncontrolled illness, Active CNS disease, Recent stroke, others

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

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: 24

Duration: Up to 8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining ibrutinib and brentuximab vedotin to treat Hodgkin's lymphoma, particularly in cases where the disease has returned or resisted other treatments. Ibrutinib blocks enzymes that aid cancer cell growth, while brentuximab vedotin (Adcetris) assists the immune system in attacking these cells. Patients whose Hodgkin's lymphoma has not responded to at least one previous treatment or has recurred may be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents, certain biological therapies, or strong CYP3A4/5 inhibitors. 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?

Previous studies have shown that using ibrutinib with brentuximab vedotin results in more side effects than using brentuximab vedotin alone. Brentuximab vedotin, an approved treatment for Hodgkin lymphoma, is usually well-tolerated. However, combining it with ibrutinib, which blocks certain enzymes to stop cancer growth, can increase side effects. Patients might experience more negative effects with the combination than with brentuximab vedotin alone.

These findings suggest that while the combination might be more effective, it could also pose more risks. Participants should be aware of these possible side effects when considering joining the trial. Consulting a healthcare provider for personalized advice is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Ibrutinib combined with Brentuximab Vedotin for Hodgkin's Lymphoma because these drugs offer a fresh approach to tackling the disease. Ibrutinib works by inhibiting a specific enzyme (BTK) crucial for the survival of cancer cells, which is different from traditional chemotherapy that targets rapidly dividing cells more broadly. Brentuximab Vedotin, on the other hand, is an antibody-drug conjugate that delivers a potent toxin directly to cancer cells, sparing normal cells. This combination has the potential to enhance effectiveness and reduce side effects compared to the usual chemotherapy treatments.

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

This trial will evaluate two different dosages of ibrutinib combined with brentuximab vedotin for treating relapsed or refractory Hodgkin's Lymphoma. Studies have shown that ibrutinib with brentuximab vedotin is about as effective as brentuximab vedotin alone. While this combination can combat the cancer, it also causes more side effects than using brentuximab vedotin by itself. Brentuximab vedotin has shown success with other treatments, achieving high response rates in Hodgkin's Lymphoma. Ibrutinib blocks certain enzymes that cancer cells need to grow, while brentuximab vedotin aids the immune system in attacking the cancer. Despite its potential, the significant side effects of the combination may limit its future use. ^{2 3 5 6 7}

Who Is on the Research Team?

Alex Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory Hodgkin lymphoma, who have tried at least one treatment before. They must have a certain level of blood cells and organ function, agree to use contraception, and not be pregnant. People can't join if they weigh less than 40 kg, have severe illnesses or infections, are on certain drugs that affect the liver enzyme CYP3A4/5, or had bad reactions to similar drugs.

Inclusion Criteria

My hemoglobin level is at least 8.5 g/dl, and I haven't used growth factors in the last 14 days.

My cancer can be measured and is larger than 1.5 cm on a CT or PET scan.

My platelet count is at least 50,000/uL, and I haven't used growth factors in the last 14 days.

Exclusion Criteria

I haven't had a heart attack in the last 6 months and don't have severe heart issues.

I weigh 40 kg or less.

I don't have any severe illnesses that could risk my safety in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily and brentuximab vedotin intravenously every 21 days

Up to 8 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Ibrutinib

Trial Overview The trial tests combining Ibrutinib (which blocks enzymes for cell growth) with Brentuximab Vedotin (an antibody that helps the immune system attack cancer). It's for patients whose Hodgkin lymphoma has come back after treatment or hasn't responded to previous treatments.

How Is the Trial Designed?

Group I: Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days Experimental Treatment 2 Interventions

Patients receive ibrutinib 560 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days Experimental Treatment 2 Interventions

Patients receive ibrutinib 420 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9642064/

P112: Phase II Trial of Brentuximab Vedotin plus ibrutinib ... The combination of BV and Ibr had similar efficacy to BV monotherapy in patients with r/r HL, but with additional toxicity compared to BV alone.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02744612

Ibrutinib and Brentuximab Vedotin in Treating Patients With ... This phase II trial studies how well ibrutinib and brentuximab vedotin work in treating patients with Hodgkin lymphoma that has returned (relapsed) or does ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38693037/

Brentuximab Vedotin Plus Ibrutinib in Relapsed and ... The combination of BV and ibrutinib was active in r/r HL; however, given significant toxicity, it cannot be recommended for future development.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0305737223001408

Antibody based therapies in Hodgkin lymphoma A chemo-sparing combination regimen of BV and Nivolumab was tested in a phase 1/ 2 study recently and reported an ORR of 85 % (CR: 67 %) and a 3-year PFS of 77 ...

5. withpower.com withpower.com/trial/phase-2-lymphoma-8-2017-82d27

Brentuximab Vedotin + Chemotherapy for Hodgkin's ... Research shows that Brentuximab Vedotin, when combined with chemotherapy, has been effective in treating Hodgkin's Lymphoma, with high response rates in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6130098/

Update on the role of brentuximab vedotin in classical ... Brentuximab vedotin (BV) is an effective and well-tolerated treatment for patients with classical Hodgkin lymphoma (HL). It was initially approved by the US FDA ...

7. ashpublications.org ashpublications.org/blood/article/125/9/1394/34206/Brentuximab-vedotin-demonstrates-objective

Brentuximab vedotin demonstrates objective responses in a ... Brentuximab vedotin was active in DLBCL across a range of CD30 expression levels, and objective responses occurred in 44% of patients.