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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + Durvalumab for Central Nervous System Lymphoma

Phase 1

Recruiting

Led By Neha Mehta-Shah, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

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

Must have

Age ≥ 18 years

Body weight >30 kg

Must not have

Active concurrent malignancy requiring active therapy

Patient requires more than 8 mg of dexamethasone daily or the equivalent for control of CNS symptoms at the time of initiation of study therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up completion of first 12 weeks of treatment within phase i portion of study (estimated to be 14 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two different types of drugs to treat people with primary central nervous system lymphoma, a cancer of the lymph nodes in the brain and spinal cord. The study has enrolled three patients so far, but all three had a different type of CNS lymphoma (secondary, not primary) and they all progressed quickly despite treatment. So the study is being amended to only include patients with primary CNS lymphoma.

Who is the study for?

This trial is for adults over 18 with primary CNS lymphoma that's relapsed or resistant to treatment, or those who can't have high-dose methotrexate therapy. Participants need a certain level of white blood cells and organ function, no HIV, and must not be pregnant. They should be able to perform daily activities with little to no assistance (ECOG status 0-2). People with secondary CNS lymphoma or recent other treatments are excluded.

What is being tested?

The study tests Acalabrutinib combined with Durvalumab in patients with primary central nervous system lymphoma. It aims to see if this drug combo is effective when standard therapies fail or aren't suitable. The trial was adjusted after finding the combination less effective in secondary CNS lymphoma cases.

What are the potential side effects?

Possible side effects include severe neutropenia (low white blood cell count), which increases infection risk; pneumonia; worsening heart disease; and potentially others related to immune response due to Durvalumab's action on the body's checkpoint mechanisms.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I weigh more than 30 kilograms.

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My platelet count is healthy and I haven't had a platelet transfusion in the last week.

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My eye condition does not involve only the vitreous.

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My brain lymphoma has returned or didn't respond to treatment, and I've tried at least one therapy.

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I have had treatment directly into my spinal fluid for cancer spread to the brain or spine.

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My cancer can be measured or observed.

Exclusion Criteria

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

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I am currently receiving treatment for another cancer.

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I need more than 8 mg of dexamethasone daily for my CNS symptoms.

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I am suspected of or confirmed to have PML.

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I have not had brain radiation in the last 14 days.

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I am not taking strong drugs that affect liver enzyme CYP3A.

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I have had a serious fungal infection or active tuberculosis.

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I cannot swallow pills.

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I am taking Warfarin or similar blood thinners.

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I have a serious gut condition that affects how I absorb pills.

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I have an active hepatitis B or C infection.

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I have been diagnosed with HIV.

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I have a bleeding disorder or am currently experiencing active bleeding.

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I am not using any cancer treatment drugs other than corticosteroids.

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I haven't had major surgery in the last 28 days and don't plan to have any within 2 weeks of starting the trial.

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I have been treated with a BTK inhibitor before.

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I have previously been treated with a checkpoint inhibitor like durvalumab.

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I need medication for stomach acid.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ completion of first 12 weeks of treatment within phase i portion of study (estimated to be 14 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~completion of first 12 weeks of treatment within phase i portion of study (estimated to be 14 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and completion of first 12 weeks of treatment within phase i portion of study (estimated to be 14 months) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Tolerability as defined as tolerable dose

Secondary study objectives

Duration of response

Overall response rate (complete response (CR) + partial response (PR))

Overall survival (OS)

+2 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

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: Phase I Dose Level 2: Durvalumab + AcalabruitinibExperimental Treatment2 Interventions

* Acalabrutinib 200 mg twice per day by mouth on days 1-28 * Durvalumab 1500 mg intravenous on day 1 of a 28 day cycle

Group II: Phase I Dose Level 1: Durvalumab + AcalabruitinibExperimental Treatment2 Interventions

* Acalabrutinib 100 mg twice per day by mouth on days 1-28 * Durvalumab 1500 mg intravenous on day 1 of a 28 day cycle

Group III: Expansion Cohort: Durvalumab + AcalabrutinibExperimental Treatment2 Interventions

* Acalabrutinib 100 mg or 200 mg (depends on tolerable dose found in Phase I portion of study) twice per day by mouth on days 1-28 * Durvalumab 1500 mg intravenous on day 1 of a 28 day cycle

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 4

~3880

Acalabrutinib

2020

Completed Phase 2

~2110