What is the mechanism of action of this treatment?

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include Bruton's Tyrosine Kinase (BTK) inhibitors like acalabrutinib and combination therapies such as R-CHOP. BTK inhibitors block the BTK enzyme, essential for B-cell survival and proliferation, thereby inhibiting lymphoma growth. R-CHOP combines rituximab, which targets CD20 on B-cells leading to their destruction, with chemotherapeutic agents that damage DNA and inhibit cell division. Understanding these mechanisms helps in selecting effective treatments tailored to the specific lymphoma type, improving patient outcomes and reducing side effects.

What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, particularly BTK inhibitors like Acalabrutinib, Ibrutinib, and Zanubrutinib, are associated with several side effects. Acalabrutinib is generally better tolerated than Ibrutinib, with fewer instances of cardiotoxicity. Common side effects of Acalabrutinib include headache, diarrhea, nausea, and infections. Serious adverse events can include atrial fibrillation, hypertension, and major bleeding. Ibrutinib, while effective, has a higher incidence of bleeding, atrial fibrillation, and hypertension. Zanubrutinib shares a similar side effect profile but is noted for its balance of efficacy and tolerability.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Hodgkin's Lymphoma (NHL), including Bruton's Tyrosine Kinase (BTK) inhibitors like ibrutinib and acalabrutinib. Ibrutinib, approved for various types of NHL, works by inhibiting BTK, a key enzyme in the B-cell receptor signaling pathway, thereby reducing cancer cell proliferation. Acalabrutinib, another BTK inhibitor, has shown efficacy in treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), and is being studied in combination with R-CHOP for diffuse large B-cell lymphoma (DLBCL). Other approved treatments include rituximab, a monoclonal antibody targeting CD20 on B-cells, often used in combination with chemotherapy regimens like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These therapies have significantly improved response rates and overall survival in patients with NHL.

What other types of research exist?

Promising alternatives to Acalabrutinib for Non-Hodgkin's Lymphoma patients include other BTK inhibitors such as Ibrutinib and Zanubrutinib. Additionally, novel therapies like CAR T-cell therapy (e.g., Axicabtagene Ciloleucel) and bispecific antibodies (e.g., Mosunetuzumab) are emerging as effective treatments. These options have shown significant efficacy in clinical trials and are expected to be viable alternatives in 2024.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + R-CHOP for Diffuse Large B-Cell Lymphoma (ESCALADE Trial)

Phase 3

Waitlist Available

Research Sponsored by Acerta Pharma BV

Eligibility Criteria Checklist

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

Must have

Disease Stage II to IV by the Ann Arbor Classification

Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review

Must not have

Uncontrolled active systemic fungal, bacterial, viral, or other infection

History of or ongoing confirmed PML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial tests if adding acalabrutinib to the standard R-CHOP chemotherapy is more effective for patients aged 75 or younger with untreated non-germinal center diffuse large B-cell lymphoma. Acalabrutinib blocks a protein that helps cancer cells grow, while R-CHOP uses multiple drugs to kill cancer cells.

Who is the study for?

This trial is for men and women aged 18-70 with previously untreated non-GCB DLBCL, a type of lymphoma. Participants must have an ECOG performance status ≤2, IPI score of 1 to 5, and Stage II to IV disease. They need adequate organ function and agree to use contraception during the study plus one year after.

What is being tested?

The trial tests acalabrutinib combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) against a placebo plus R-CHOP in patients under 75 years old. It's randomized and double-blind to compare effectiveness and safety.

What are the potential side effects?

Possible side effects include reactions related to infusion such as fever or chills; low blood counts leading to increased infection risk; nausea; hair loss from chemotherapy drugs like doxorubicin; nerve damage from vincristine causing numbness or tingling.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is classified as Stage II to IV.

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My diagnosis of DLBCL is confirmed and samples can be sent for further testing.

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I am between 18 and 70 years old.

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I have not received any treatment for DLBCL.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

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

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I do not have any untreated serious infections.

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I have been diagnosed with or currently have PML.

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I have not had a stroke or brain bleed in the last 6 months.

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My lymphoma has specific genetic changes known as MYC, BCL2, and/or BCL6.

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I do not have major issues with my stomach or intestines that affect how I absorb food or medicine.

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I have a known bleeding disorder.

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I have been diagnosed with lymphoma in the area between my lungs.

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I have received a high dose of anthracycline.

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I do not have serious heart problems like recent heart attacks or uncontrolled heart rhythm issues.

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I have cancer in my brain or spinal cord.

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I have a history of slow-growing lymphoma or chronic lymphocytic leukemia.

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I have a severe illness that is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2016 Phase 2 trial • 31 Patients • NCT02387762

13%

Anaemia

Musculoskeletal chest pain

Dizziness

Nausea

Oedema peripheral

Thrombocytosis

Full Blood Count decreased

Leukopenia

Hyponatraemia

Haematuria

Intervertebral disc degeneration

Contusion

Hypochloraemia

Vomiting

Diarrhea

100%

80%

60%

40%

20%

Study treatment Arm

ACP-196 + Methotrexate

Placebo + Methotrexate

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: acalabrutinib + R-CHOPExperimental Treatment6 Interventions

Acalabrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Group II: placebo + R-CHOPPlacebo Group6 Interventions

Placebo plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Doxorubicin

2012

Completed Phase 3

~8030

Vincristine

2003

Completed Phase 4

~2970

acalabrutinib

2018

Completed Phase 2

~80

Prednisone

2014

Completed Phase 4

~2500

Rituximab

1999

Completed Phase 4

~2990

Cyclophosphamide

2010

Completed Phase 4

~2310

0 / 17Eligibility 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 Non-Hodgkin's Lymphoma (NHL) include Bruton's Tyrosine Kinase (BTK) inhibitors like acalabrutinib and combination therapies such as R-CHOP. BTK inhibitors block the BTK enzyme, essential for B-cell survival and proliferation, thereby inhibiting lymphoma growth. R-CHOP combines rituximab, which targets CD20 on B-cells leading to their destruction, with chemotherapeutic agents that damage DNA and inhibit cell division. Understanding these mechanisms helps in selecting effective treatments tailored to the specific lymphoma type, improving patient outcomes and reducing side effects.

The treatment of Burkitt lymphoma in adults.