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Central Nervous System LymphomaPhase 1/2NCT04906902

Acalabrutinib in CNSL

A Phase 1/2 study testing Acalabrutinib in people with Central Nervous System Lymphoma and Refractory Central Nervous System Lymphoma, run by Dana-Farber Cancer Institute at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
3 sitesUnited States
Study dates
23 Aug 2021to 31 Jan 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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
  • Absolute Neutrophil Count ≥ 1.5 K/µL
  • Hemoglobin > 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
  • Serum creatinine ≤1.5 x institutional ULN OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (Creatinine clearance should be calculated per institutional standard)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤5 × ULN for participants with liver metastases)
  • Total bilirubin (TBILI) ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x institutional ULN) OR Direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN)
  • Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib. For male subjects with a pregnant or non-pregnant WOCBP partner, no contraception measures are required. Highly effective methods of contraception include:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal
  • Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
  • Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomy of a female subject's male partner (with medical assessment and confirmation of vasectomy surgical success)
  • Sexual abstinence (only if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments)

Who cannot join

  • 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.
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  • 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.
  • Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
  • History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
  • Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded.
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded.
  • Breast feeding or pregnant
  • Concurrent participation in another therapeutic trial.
  • Liver cirrhosis categorized at Child Pugh Score C.
  • Uncontrolled hypertension despite optimal medical management.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Acalabrutinib in Recurrent or Refractory Central Nervous System Lymphoma (CNSL)

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).

Read the detailed description

This is an open-label, dose-escalation phase 1/2 study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Acalabrutinib in patients with recurrent or refractory CNS lymphoma (R/R CNSL).

Acalabrutinib has been studied in lab experiments and in other types of cancer, and information from these studies suggests that acalabrutinib may be beneficial for people with recurrent or refractory central nervous system lymphoma (CNSL). Acalabrutinib targets a vulnerable part of cancer cells which leads to an inhibition of the growth of cancer cells.

The U.S. Food and Drug Administration (FDA) has not approved acalabrutinib for recurrent or refractory central nervous system lymphoma (CNSL) but it has been approved for other uses.

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive study treatment for up to 2 years as long as they do not have serious side effects and their disease does not get worse.

Approximately 15 to 21 participants will be enrolled in phase1 and approximately 28 patients will be enrolled Phase 2.

AstraZeneca, a pharmaceutical company, is supporting this research study by providing funding for the research study and the study drug, acalabrutinib.

Being tested
Acalabrutinib
Keywords
Central Nervous System Lymphoma, Refractory Central Nervous System Lymphoma, Recurrent Central Nervous System Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called Calquence

    Tablet taken by mouth twice daily

Study groups in NCT04906902
Study groupRoleWhat they receive
Acalabrutinib Dose EscalationExperimentalPhase 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
Receives: Drug: Acalabrutinib
Acalabrutinib Dose ExpansionExperimentalPhase 2 Participants will receive Acalabrutinib at the pre-determined dosage established in Phase 1.
Receives: Drug: Acalabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Enrollment to end of treatment up to 2 years

Secondary outcomes (5)

  1. Objective response rate (ORR).

    Clinical assessment and International Primary cns lymphoma Collaborative Group (IPCG) criteria (Abrey, 2005)

    Measured: Enrollment to end of treatment up to 2 years

  2. Duration of response (DOR)

    Clinical assessment and International Primary cns lymphoma Collaborative Group (IPCG) criteria (Abrey, 2005)

    Measured: Every 8 weeks up to 2 years

  3. Progression-free survival (PFS)

    Evaluated by the Kaplan-Meier method and medians will be provided with 95% CI

    Measured: Enrollment to end of treatment up to 2 years

  4. Overall survival (OS)

    Evaluated by the Kaplan-Meier method and medians will be provided with 95% CI

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

  5. Treatment-related toxicity

    Assessed by CTCAE version 5.0.

    Measured: Enrollment to end of treatment up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2021
  2. Study start23 Aug 2021
  3. Primary completion6 Nov 2025
  4. Study completion31 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04906902
Sponsor's protocol ID
21-059
Status last verified
Jun 2026
First submitted
25 May 2021
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Acalabrutinib in people with Central Nervous System Lymphoma and Refractory Central Nervous System Lymphoma, run by Dana-Farber Cancer Institute at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum-tolerated dose (MTD) (time frame: Enrollment to end of treatment up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04906902.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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