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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + CAR T-cell Therapy for B-Cell Lymphoma

Phase 1 & 2

Recruiting

Led By Ajay Gopal

Research Sponsored by University of Washington

Eligibility Criteria Checklist

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

Must have

Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, and indolent (grade 1-3a) FL

Creatine clearance (CrCl) > 50 mL/min or serum creatinine =< 2.5

Must not have

Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded

Active and uncontrolled systemic or clinically significant infection that would contraindicate myelosuppressive therapy or CART infusion

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of a new combination therapy for B-cell lymphoma. The treatment involves acalabrutinib, which may stop the growth of tumor cells, and axicabtagene ciloleucel, which is an immunotherapy that targets a specific surface antigen on lymphoma cells.

Who is the study for?

Adults with B-cell lymphoma eligible for axi-cel per FDA, understanding and consenting to the study, ECOG status of 0-1, adequate organ function, no active infections or second cancers needing treatment. Excludes those intolerant to acalabrutinib, with brain metastases or cerebrospinal fluid malignant cells, on strong CYP3A inhibitors/inducers, refractory to BTK inhibition, low blood counts, pregnant/breastfeeding women.

What is being tested?

The trial is testing the combination of acalabrutinib (a drug that blocks tumor growth pathways) and axicabtagene ciloleucel (a CAR T-cell therapy targeting lymphoma cells). It aims to see if acalabrutinib can boost the effectiveness of the immunotherapy in treating B-cell lymphoma.

What are the potential side effects?

Potential side effects include immune system reactions due to CAR T-cell therapy such as fever and difficulty breathing; acalabrutinib may cause bleeding issues or heart rhythm problems. Side effects vary by individual.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with a specific type of large B-cell lymphoma.

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My kidney function is good, with a creatinine clearance over 50 mL/min or serum creatinine <= 2.5.

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I breathe well with minimal shortness of breath and my oxygen level is above 92% without assistance.

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I meet the FDA requirements for axi-cel treatment.

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I am HIV positive and do not have any uncontrolled infections.

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My heart pumps well and I don't have fluid around it.

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I can understand and sign the consent form.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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I am HIV positive without any current severe infections needing antibiotics.

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I am HIV positive with a hemoglobin level above 8.0 g/dl.

Exclusion Criteria

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

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I do not have active hepatitis B as confirmed by negative tests.

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I do not have any serious infections that would make treatment risky.

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I have not had major surgery in the last 7 days or have fully recovered from it.

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I have or had cancer cells in my brain or spinal fluid.

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I cannot swallow pills or have a condition affecting my stomach or intestines that impacts how I absorb medication.

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I have a history of seizures, stroke, memory disorders, or autoimmune diseases affecting my brain.

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I do not have active bleeding or a history of bleeding disorders like hemophilia.

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My condition did not improve with BTK inhibitor treatment.

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I haven't taken strong CYP3A drugs in the last week and don't need them now.

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I have uncontrolled AIHA or ITP.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years post treatment

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

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Secondary study objectives

Complete response rate following chimeric antigen receptor T-cells therapy (CART)

Response rate

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

1Treatment groups

Experimental Treatment

Group I: Treatment (acalabrutinib, axicabtagene ciloleucel)Experimental Treatment2 Interventions

Beginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib PO every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel IV at 36-96 hours after completion of lymphodepleting chemotherapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acalabrutinib

2020

Completed Phase 2

~2080

Axicabtagene Ciloleucel

2020

Completed Phase 2

~510