What side effects are associated with this type of intervention?

Common treatments for Waldenstrom Macroglobulinemia, such as bendamustine and rituximab, are associated with several side effects. Bendamustine can cause infusion reactions, fatigue, nausea, and myelosuppression, leading to low blood cell counts. Rituximab is known for infusion-related reactions, which can be severe, especially during the first cycle, and may include fever, chills, and respiratory symptoms. BTK inhibitors like Acalabrutinib can cause headaches, diarrhea, muscle pain, and increased risk of infections. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Waldenstrom Macroglobulinemia, including BTK inhibitors like Ibrutinib, which was the first in its class to receive approval for this condition. Ibrutinib works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme in the B-cell receptor signaling pathway, which is crucial for the survival and proliferation of malignant B cells. Other treatments include rituximab, a monoclonal antibody targeting CD20 on B cells, often used in combination with chemotherapy agents like bendamustine. These treatments aim to reduce the burden of malignant cells and manage symptoms effectively.

What other types of research exist?

Promising alternatives to Acalabrutinib for Waldenstrom Macroglobulinemia patients include Zanubrutinib and Ibrutinib, both of which are BTK inhibitors with demonstrated efficacy in WM. Additionally, combination therapies involving BTK inhibitors with other agents like rituximab or venetoclax are being explored and may offer enhanced treatment outcomes.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + Chemotherapy for Waldenstrom's Macroglobulinemia (BRAWM Trial)

Phase 2

Waitlist Available

Led By Neil L Berinstein, MD

Research Sponsored by Sunnybrook Health Sciences Centre

Eligibility Criteria Checklist

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

Must have

Have symptomatic or impending symptomatic disease or evidence of hematologic or biochemical compromise related to the lymphoma

Have at least one measurable site of disease based on Cheson Criteria (Appendix C) using standard CT imaging or a quantifiable IgM paraprotein that is two times the upper limit of normal

Must not have

Has a known history of active TB (Bacillus Tuberculosis)

Previous systemic therapy for WM (other than described in the inclusion criteria)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 year post first dose

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial tests a combination of two established drugs and one new drug in untreated patients with a specific type of blood cancer. The treatment works by killing cancer cells, boosting the immune system, and blocking growth signals.

Who is the study for?

This trial is for adults with untreated Waldenstrom's Macroglobulinemia, a type of lymphoma. Participants must have a life expectancy over 6 months, be willing to use effective birth control methods, and have adequate organ function. They should not have had previous systemic treatments for the disease (except certain allowed therapies) and must be able to comply with study requirements.

What is being tested?

The trial tests Acalabrutinib in combination with standard-of-care Bendamustine and Rituximab in patients who haven't been treated before. It's an open-label phase II study where participants receive Bendamustine intravenously on two days per cycle, Rituximab either intravenously or subcutaneously once per cycle, and take Acalabrutinib orally twice daily for one year.

What are the potential side effects?

Potential side effects include infusion reactions from Bendamustine and Rituximab such as fever or chills; low blood counts leading to increased infection risk; nausea; fatigue; bruising or bleeding due to Acalabrutinib. Organ inflammation could also occur due to immune system activation by these drugs.

Eligibility Criteria

Inclusion Criteria

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

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My lymphoma is causing symptoms or is about to cause symptoms.

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My cancer can be measured by scans or blood tests.

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I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of active tuberculosis.

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I have had treatment for Waldenstrom macroglobulinemia before.

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My high blood pressure cannot be controlled with medication.

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I have severe stomach issues that prevent me from properly absorbing medication.

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I have had lung inflammation not caused by infection, treated within the last 5 years.

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I am not willing to stop or change my warfarin or proton pump inhibitor medication before joining.

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

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I have not had major surgery in the last 30 days or have fully recovered if I did.

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I have a bleeding disorder like hemophilia.

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I have been diagnosed with HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 year post first dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 year post first dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 year post first dose for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Best combined complete response (CR) and very good partial response (VGPR)

Secondary study objectives

Documentation of minimal residual disease (MRD) rate

Documentation of overall survival

Documentation of progression free survival

+4 more

Side effects data

From 2020 Phase 2 trial • 177 Patients • NCT04346199

Headache

Septic shock

Ischaemic stroke

Chronic obstructive pulmonary disease

100%

80%

60%

40%

20%

Study treatment Arm

BSC Alone

Acalabrutinib + BSC

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

1Treatment groups

Experimental Treatment

Group I: Single arm interventionExperimental Treatment3 Interventions

100 mg Acalabrutinib (ACP-196) oral capsules twice daily for 1 year Bendamustine and rituximab will be given for 6 x 28-day cycles. Bendamustine will be given intravenously at 90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously for the first cycle and 1400 mg subcutaneously OR 375 mg/m2 intravenously for subsequent cycles (as per institutional procedures).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bendamustine

FDA approved

Acalabrutinib

FDA approved

Rituximab

FDA approved

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Waldenstrom Macroglobulinemia (WM) include BTK inhibitors like Acalabrutinib, which block Bruton's tyrosine kinase (BTK), a key enzyme in the B-cell receptor signaling pathway. This inhibition disrupts the growth and survival of malignant B-cells. Additionally, treatments like bendamustine and rituximab target WM cells through different mechanisms: bendamustine is an alkylating agent that damages DNA, leading to cell death, while rituximab is a monoclonal antibody that targets CD20 on B-cells, marking them for destruction by the immune system. These treatments are crucial for WM patients as they directly interfere with the pathways and cellular mechanisms that allow the cancer to thrive, thereby controlling disease progression and improving patient outcomes.