Acalabrutinib and Durvalumab in Primary and Secondary Central Nervous System Lymphoma

Part of paid clinical trials in St Louis, Missouri.

Sponsor
Washington University School of Medicine
Study ID
NCT04462328
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Durvalumab will be administered over 60 minutes
  • Acalabrutinib — DRUG
    Patients will take acalabrutinib orally every 12 hours (+/- 3 hours) daily.

Study Details

BTK inhibition and checkpoint blockade are promising classes of therapy for central nervous system (CNS) lymphoma and have demonstrated efficacy with acceptable toxicity. A multidrug approach may carry a higher chance of durable efficacy in this aggressive disease that carries significant morbidity and mortality. Given the poor outcomes and limited options for patients who are not candidates for high-dose methotrexate, the investigators seek to evaluate the combination in this patient population. 08/30/2022: The study was originally designed for those with primary and secondary central nervous system (CNS) lymphoma. However, the first three patients who were enrolled all had secondary CNS lymphoma and most had germinal center phenotype disease with double hit phenotypes. In these three patients, two dose limiting toxicities were seen including 1 patient with grade 4 neutropenia at the time of disease progression and one with pneumonia in the setting of disease progression and worsening of existing heart disease. The third patient came off for clinical progression within cycle 1. Given the lack of response in patients with secondary CNS lymphomas, who do not exhibit the same biology as primary CNS lymphoma patients, Amendment 3 updates the study to only include patients with primary CNS lymphomas.

Key Dates

Start date
Apr 29, 2021
Status verified
Mar 2026
Primary completion
Aug 31, 2026
Completion
May 31, 2028

Study Design

Enrollment
25 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I Dose Level 1: Durvalumab + Acalabruitinib
    * Acalabrutinib 100 mg twice per day by mouth on days 1-28 * Durvalumab 1500 mg intravenous on day 1 of a 28 day cycle
  • Experimental: Phase I Dose Level 2: Durvalumab + Acalabruitinib
    * Acalabrutinib 200 mg twice per day by mouth on days 1-28 * Durvalumab 1500 mg intravenous on day 1 of a 28 day cycle
  • Experimental: Expansion Cohort: Durvalumab + Acalabrutinib
    * 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

Primary Outcome Measure

Tolerability as defined as tolerable dose [ Time Frame: Completion of first 12 weeks of treatment within phase I portion of study (estimated to be 14 months) ]

Locations (2)

FacilityCityStateZIPSite coordinators
Washington University School of MedicineSt LouisMissouri63110-
The Ohio State University HospitalColumbusOhio43210-

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By research site
Washington University School of Medicine· St Louis, MOThe Ohio State University Hospital· Columbus, OH

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