Chemotherapy Combinations for Mantle Cell Lymphoma

Palo Alto (17 mi)

Overseen byNina D Wagner-Johnston

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: ECOG-ACRIN Cancer Research Group

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This phase II trial compares three chemotherapy regimens consisting of bendamustine, rituximab, high dose cytarabine, and acalabrutinib and studies how well they work in treating patients with newly diagnosed mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study is being done to find out if one the drug combinations of bendamustine, rituximab, high dose cytarabine, and acalabrutinib is better or worse than the usual approach for mantle cell lymphoma.

Eligibility Criteria

This trial is for adults with newly diagnosed mantle cell lymphoma. Participants should be in good physical condition (ECOG score 0-2), have acceptable blood counts, liver and kidney function, and not be pregnant or breastfeeding. They must agree to use contraception and cannot have certain heart conditions, active infections, bleeding disorders, severe allergies to the drugs being tested, or be on specific medications that affect drug metabolism.

Inclusion Criteria

Patients are ineligible if they have any of the following: Malabsorption syndrome or disease significantly affecting gastrointestinal function, Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease), Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenia purpura), Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug, History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug, Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), History of severe allergic reaction attributed to compounds of similar chemical or biologic composition to rituximab, bendamustine, cytarabine, or acalabrutinib

I haven't taken strong or moderate CYP3A inhibitors or inducers in the last week.

I am able to care for myself and perform daily activities.

I agree to use effective birth control or abstain from sex during and for 12 months after the study.

My hepatitis B virus is under control with treatment.

You are not eligible for the study if you have any of the following conditions: problems with absorbing nutrients, a history of bleeding disorders or anemia, autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura that is not under control, taking blood thinners such as warfarin within 7 days of starting the study drug, significant cerebrovascular disease or events within 6 months before starting the study drug, active infections that are not responding to treatment, severe allergic reaction to similar drugs like rituximab, bendamustine, cytarabine, or acalabrutinib.

My lymphoma is confirmed to be mantle cell type with specific genetic markers.

I am not on strong medications that affect liver enzyme CYP3A.

I can provide a tissue sample from my initial diagnosis or a blood sample for the study.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I can take care of myself and am up and about more than half of my waking hours.

My hepatitis B virus load is undetectable with treatment.

I haven't taken strong or moderate CYP3A inhibitors or inducers in the last week.

I agree to use effective birth control or abstain from sex during and for 12 months after the study.

My lymphoma is confirmed to be mantle cell type with specific genetic markers.

I am not on strong medication that affects liver enzyme CYP3A.

I will switch from proton pump inhibitors before starting acalabrutinib.

My lymphoma is only in my liver and can be measured.

I will switch from proton pump inhibitors before starting acalabrutinib.

Treatment Details

The study compares three chemotherapy regimens using bendamustine, rituximab, high dose cytarabine, and acalabrutinib to see which works best for treating mantle cell lymphoma. It aims to determine if these combinations are more effective than current treatments by stopping cancer cells from growing.

3Treatment groups

Experimental Treatment

Group I: Arm C (acalabrutinib, bendamustine, rituximab)Experimental Treatment4 Interventions

Patients receive acalabrutinib PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (acalabrutinib, bendamustine, rituximab, cytarabine)Experimental Treatment5 Interventions

Patients receive PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive acalabrutinib PO BID on days 1-7 and 22-28, rituximab IV on day 1, and cytarabine IV Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm A (bendamustine, rituximab, cytarabine)Experimental Treatment4 Interventions

Patients receive bendamustine IV on days 1 and 2 and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive rituximab IV on day 1 and cytarabine IV every Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

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

🇺🇸 Approved in United States as Calquence for: