Acalabrutinib + Chemotherapy for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: BTK inhibitors, Strong CYP3A4 inhibitors, Warfarin, Proton pump inhibitors

Disqualifiers: Chemotherapy, Brain lymphoma, Cardiovascular, 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: 1

Duration: 6 months

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to evaluate the efficacy and safety of acalabrutinib plus bendamustine and rituximab followed by acalabrutinib plus cytarabine and rituximab in subjects with treatment naïve mantle cell lymphoma (MCL), as a preparation for a larger cooperative group trial with the goal of achieving a standard induction regimen for MCL in transplant eligible patients. The investigators hypothesize that the addition of acalabrutinib to BR/CR regimen will prove safe and increase the complete response (CR) rate as well as minimal residual disease (MRD) negativity pre-transplant, thus improving clinical outcomes.

Research Team

Brad S. Kahl

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults aged 18-70 with untreated mantle cell lymphoma who are eligible for stem cell transplantation. Participants must have adequate organ and bone marrow function, no history of significant bleeding disorders or major surgery within the last month, and not be on certain medications like strong CYP3A4 inhibitors or proton pump inhibitors. Pregnant or breastfeeding women cannot join.

Inclusion Criteria

- Absolute neutrophil count ≥ 1,000/mcL unless, in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement

Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

I am eligible for a stem cell transplant using my own cells.

Exclusion Criteria

I have not had a live virus vaccine in the last 28 days.

I am allergic to certain medications used in this study.

I need medication that strongly affects liver enzyme levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib plus bendamustine and rituximab for Cycles 1-3, followed by acalabrutinib plus cytarabine and rituximab for Cycles 4-6

6 months

Cycles 1-3: Bendamustine on Days 1 and 2, Rituximab on Day 1, Acalabrutinib BID on Days 1-28; Cycles 4-6: Rituximab on Day 1, Cytarabine every 12 hours on Days 1 and 2, Acalabrutinib BID on Days 1-7 and 22-28

Leukapheresis

Patients undergo leukapheresis after completion of Cycle 6

Up to 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Through 5 years

Treatment Details

Interventions

• Acalabrutinib
• Bendamustine
• Cytarabine
• Rituximab

Trial Overview The study tests acalabrutinib combined with bendamustine/rituximab followed by cytarabine/rituximab in patients with mantle cell lymphoma. The goal is to see if this regimen before a stem cell transplant can improve response rates and outcomes compared to current treatments.

Participant Groups

Group I: Bendamustine/Rituximab/Acalabrutinib/Cytarabine Experimental Treatment 8 Interventions

* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis

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

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Acerta Pharma BV

Industry Sponsor

Trials

46

Recruited

5,900+