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Bruton's Tyrosine Kinase (BTK) Inhibitor

Chemotherapy Combinations for Mantle Cell Lymphoma

Phase 2

Waitlist Available

Led By Nina D Wagner-Johnston

Research Sponsored by ECOG-ACRIN Cancer Research Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Patients may not have received the following within 7 days prior to the first dose of study drug: Strong and moderate CYP3A inhibitors, Strong and moderate CYP3A inducers.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years post randomization

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing different combinations of chemotherapy drugs and monoclonal antibodies to treat mantle cell lymphoma.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at the infusion site; low blood counts leading to increased infection risk; fatigue; nausea; liver issues; allergic reactions; potential heart problems due to some of the drugs used in treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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

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My hepatitis B virus is under control with treatment.

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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.

Select...

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

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

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

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

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

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

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My hepatitis B virus load is undetectable with treatment.

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

Select...

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

Select...

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

Select...

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

Select...

I will switch from proton pump inhibitors before starting acalabrutinib.

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

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I will switch from proton pump inhibitors before starting acalabrutinib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years post randomization

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years post randomization

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 years post randomization for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Composite of positron emission tomography (PET)/computed tomography (CT) complete response (CR) and peripheral blood (PB) minimal residual disease (MRD) negative rate

Secondary study objectives

Incidence of adverse events

Mobilization failure rate

Objective response rate (ORR)

+1 more

Other study objectives

Change of qPET parameters

Incremental prognostic value of baseline qPET to Ki67

Incremental prognostic value of baseline qPET to standard risk markers (Mantle Cell Lymphoma International Prognostic Index [MIPI])

+4 more

Side effects data

From undefined Phase 3 trial • 1734 Patients • NCT00025259

80%

Neutrophil count decreased

42%

Anemia

31%

Platelet count decreased

26%

Febrile neutropenia

18%

White blood cell decreased

16%

Infections and infestations - Other, specify

Blood and lymphatic system disorders - Other, specify

Lymphocyte count decreased

Catheter related infection

Dehydration

Abdominal pain

Mucositis oral

Vomiting

Anaphylaxis

Hypokalemia

Hypotension

Depression

Hyponatremia

Hypoxia

Myalgia

Immune system disorders - Other, specify

Dizziness

Constipation

Esophagitis

Ileus

Pain

Carbon monoxide diffusing capacity decreased

Hypoalbuminemia

Neuralgia

Peripheral sensory neuropathy

Dyspnea

Diarrhea

Typhlitis

Hyperglycemia

Headache

Seizure

Syncope

Nausea

Cardiac disorders - Other, specify

Hypophosphatemia

Bone pain

Peripheral motor neuropathy

Thromboembolic event

Hypertension

100%

80%

60%

40%

20%

Study treatment Arm

Arm III (RER With CR [ABVE-PC])

Arm I (Patients Off-therapy Before Callback-Induction Only)

Arm II (RER With CR [ABVE-PC, IFRT])

Arm IV (RER With Less Than CR [ABVE-PC, IFRT])

Arm VII (SER [ABVE-PC, IFRT])

Arm VI (SER [DECA, ABVE-PC, IFRT])

Arm V (RER With PD)

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cytarabine

FDA approved

Rituximab

FDA approved

Acalabrutinib

FDA approved

Bendamustine

FDA approved