Acalabrutinib in CNSL

NCT04906902 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-059
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is a Phase 1/2 clinical trial testing the safety, tolerance and efficacy of the drug Acalabrutinib for people with recurrent or refractory central nervous system lymphoma (CNSL).

Conditions

Refractory Central Nervous System Lymphoma; Central Nervous System Lymphoma; Recurrent Central Nervous System Lymphoma

Keywords

Central Nervous System Lymphoma; Refractory Central Nervous System Lymphoma; Recurrent Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose (MTD)

  Highest dose of acalabrutinib that did not cause a dose limiting toxicity. Dose Limiting Toxicity (DLT) rates will be summarized and 95% exact binomial confidence interval (CI) will be reported.

  Enrollment to end of treatment up to 2 years

Secondary Outcomes (5)

• Objective response rate (ORR).

  Enrollment to end of treatment up to 2 years

• Duration of response (DOR)

  Every 8 weeks up to 2 years

• Progression-free survival (PFS)

  Enrollment to end of treatment up to 2 years

• Overall survival (OS)

  Time from randomization (or registration) to death due to any cause, or censored at date last known alive.

• Treatment-related toxicity

  Enrollment to end of treatment up to 2 years

Study Arms (2)

Acalabrutinib Dose Escalation

EXPERIMENTAL

Phase 1 Dose escalation will occur using a 3+3 dose escalation approach, evaluating three separate dose levels. * Acalabrutinib 200mg 2x daily * Acalabrutinib 300mg 2x daily * Acalabrutinib 400mg 2x daily

Drug: Acalabrutinib

Acalabrutinib Dose Expansion

EXPERIMENTAL

Phase 2 Participants will receive Acalabrutinib at the pre-determined dosage established in Phase 1.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Tablet taken by mouth twice daily

Also known as: Calquence

Acalabrutinib Dose Escalation; Acalabrutinib Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be able to understand and willing to sign a written informed consent document.
• Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
• Participants must be at least 18 years old on day of signing informed consent.
• Participants must have a ECOG Performance Status 0-1 (see Appendix A).
• Life expectancy of \> 3 months (in the opinion of the investigator).
• Participants with recurrent or refractory (R/R) must have histologically confirmed DLBCL CNS lymphoma (from brain biopsy, CSF or vitreous biopsy for PCNSL/PVRL, and includes PCNSL and SCNSL) for Phase I; R/R histologically confirmed DLBCL PCNSL (from brain biopsy only) for Phase II. Participants must have received at least 1 line of CNS-directed prior therapy. There is no maximum limit on the number of prior therapies.
• Confirmation of availability of sufficient tissue from brain biopsy for correlative studies is required prior to enrollment (for phase II only).
• The following amount of archived tissue is required: At least 10 but up to 20 unstained formalin-fixed, paraffin-embedded (FFPE) slides. Histologically confirmed tissue will be required from the time of relapse or at the time of initial surgery.
• Participants must have recovered to ≤ grade 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy.
• Participants must be able to undergo MRI.
• Participants must demonstrate adequate as defined below (all screening labs should be performed within 28 days of registration but before 1st dose of study drug):
• Hematology
• White Blood Count (WBC) ≥ 2 K/µL
• Platelet count ≥ 100 K/µL

You may not qualify if:

• Participants unable to undergo MRI brain.
• Participants with \> Grade 2 intracranial hemorrhage.
• Participants with active systemic disease.
• Participants with uncontrolled intercurrent illness.
• Participants with prior exposure to BTK inhibitors
• Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 3 years.
• Participants who have received prior systemic anti-cancer therapy including investigational agents or radiotherapy within 4 weeks prior to dosing. OR 5 half-lives, whichever is shorter Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or corrected QT interval (QTc) \> 480 msec at screening. Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study.
• Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
• Known history of infection with HIV, prior history of PML or any active significant infection (eg, bacterial, viral, or fungal).
• Known history of hypersensitivity or anaphylaxis to acalabrutinib including active product or excipient components.
• Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

acalabrutinib

Study Officials

• Lakshmi Nayak, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: August 23, 2021
• Primary Completion: April 30, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)