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Primary Central Nervous System LymphomaPhase 2NCT04906096

Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL

A Phase 2 study testing PAXALISIB in people with Primary Central Nervous System Lymphoma and Non-Hodgkin Lymphoma of Extranodal Site, run by Lakshmi Nayak, MD at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This research study is studying a drug called Paxalisib (GDC-0084) as a possible treatment for primary central nervous system lymphoma (PCNSL) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PAXALISIB
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
1 Jun 2021to 1 Dec 2027
Phase
Phase 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 Karnofsky Performance Status (KPS) ≥ 70
  • Participants must have histologically confirmed R/R primary DLBCL CNS lymphoma (from brain biopsy, CSF or vitreous biopsy).
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  • Participants should have evidence of refractory or recurrent disease on MRI with measurable or evaluable enhancing disease.
  • Participants must have recovered to ≤ grade 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy; exception, participants with ≤ grade 2 neuropathy may be eligible.
  • Participant with dexamethasone requirement of ≤ 8mg/day or bioequivalent with corticosteroid usage at a stable or decreasing dose 2 weeks prior to screening.
  • Participants must be able to undergo MRI.
  • Participants must demonstrate adequate as defined below (all screening labs should be performed within 14 days of treatment initiation):
  • 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)
  • Biochemistry
  • 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)
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy within 72 hours prior to registration.
  • WOCBP who are sexually active must use highly effective methods of contraception during treatment and for 28 days after the last dose of paxalisib. For male subjects with a pregnant or non-pregnant WOCBP partner, contraception measures are required during treatment and for 28 days after the last dose of paxalisib.
  • The subject, in consultation with the investigator, will select the most appropriate method of contraception from the permitted list of contraception methods, and site personnel will instruct the subject in its consistent and correct use as needed.
  • In addition, the investigator will instruct the subject to notify the site immediately if pregnancy of the subject or their partner is known or suspected.
  • Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly and include:
  • Established use of oral, injected, or implanted hormonal methods of contraception
  • Correctly placed intrauterine device (IUD) or intrauterine system (IUS)
  • Male condom or female condom used WITH a spermicide (i.e., foam, gel, film, cream)
  • Male sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate
  • Bilateral tubal ligation or bilateral salpingectomy

Who cannot join

  • Participants unable to undergo MRI brain.
  • Participants with active systemic disease.
  • Participants with uncontrolled intercurrent illness.
  • Participants with prior exposure to mTOR/PI3K 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, superficial bladder 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 OR 5 half-lives prior to dosing, 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.
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  • Participants who have difficulty with or are unable to swallow oral medication or have 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 paxalisib including active product or excipient components.
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer which may have an effect of the metabolism of paxalisib.
  • Participants with uncontrolled medical comorbidities per investigator discretion including but not limited to interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, pre-exisiting Crohn's disease or ulcerative colitis or pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea.
  • Participants with type I diabetes mellitus, participants with uncontrolled type II diabetes mellitus,despite being on oral anti-diabetic medication. , participants with Type II diabetes mellitus that are well controlled on insulin . Uncontrolled diabetes is defined as HbA1c >9% in addition to fasting glucose>140mg/dL on at least 2 occasions within 14 days prior to registration
  • Participants with uncontrolled hypertension despite optimal medical management (per investigator's assessment).
  • 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.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lakshmi Nayak, MD contact

(617) 632-2166

Lakshmi_Nayak@dfci.harvard.edu

United States2 sites, 2 recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Lakshmi Nayak, MD

    Lakshmi Nayak, MD

    Not yet recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

    Lakshmi Nayak, MD, (617) 632-2166, Lakshmi_Nayak@dfci.harvard.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of Paxalisib (GDC-0084) in Recurrent or Refractory Primary Central Nervous System Lymphoma (PCNSL)

This research study is studying a drug called Paxalisib (GDC-0084) as a possible treatment for primary central nervous system lymphoma (PCNSL)

Read the detailed description

This is an open-label, phase 2 study to determine the efficacy of Paxalisib (GDC-0084) in 25 patients with recurrent or refractory primary central nervous system lymphoma (R/R PCNSL.

  • The name of the study drug involved in this study is Paxalisib (GDC-0084).
  • The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.
  • It is expected that about 25 participants will take part in this research study for up to 24 months as long as there is no serious side effects and disease progression.

This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved Paxalisib for this specific disease but it has been approved for other uses.

Being tested
PAXALISIB
Keywords
Primary Central Nervous System Lymphoma, Non-Hodgkin Lymphoma of Extranodal Site

What participants receive

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

  • PAXALISIBDrug

    Also called GDC-0084

    Each study treatment cycle lasts 28 days, up to 24 months. Oral, daily, dosage per protocol

Study groups in NCT04906096
Study groupRoleWhat they receive
PAXALISIBExperimentalThe research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits. * Paxalisib (GDC-0084) * Each study treatment cycle lasts 28 days, up to 24 months.
Receives: Drug: PAXALISIB

What is being measured

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

  1. Number of participants with Objective Response Rate (ORR)

    The Objective Response (ORR) is defined as a complete, unconfirmed complete or partial response as determined by the investigator assessment using IPCG criteria

    Measured: Up to 24 Months

Secondary outcomes (4)

  1. Number of participants with Durable Objective Response Rate (ORR)

    Durable ORR will be defined as confirmed objective responses (CR, uCR and PR) by IPCG criteria that are durable for ≥ 6 months

    Measured: Up to 24 Months

  2. Overall Survival

    defined from the date of the 1st dose of paxalisib to the date of death or last follow-up. If a participant is still alive, she/he will be censored on the date of last followup.

    Measured: Up to 24 Months

  3. Progression Free Survival (PFS)

    defined from the date of 1st dose of paxalisib to the date of progression based on IPCG criteria or death, if progression does not occur. All progressors will be included regardless of whether progression occurs while the participant was taking the study drug or previously discontinued the study drug

    Measured: up to 24 Months

  4. Number of cumulative treatment-emergent adverse events (TEAEs)

    Incidence of TEAEs, grade 3-5 TEAEs, SAEs (serious adverse events) and TEAEs leading to discontinuation of study treatment.

    Measured: up to 24 Months

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 start1 Jun 2021
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Dec 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04906096
Sponsor's protocol ID
21-109
Status last verified
Jul 2026
First submitted
24 May 2021
Last updated
5 Aug 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 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 2 study testing PAXALISIB in people with Primary Central Nervous System Lymphoma and Non-Hodgkin Lymphoma of Extranodal Site, run by Lakshmi Nayak, MD at 2 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 30 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 phase mean?

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?

Contact Lakshmi Nayak, MD ((617) 632-2166, Lakshmi_Nayak@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with Objective Response Rate (ORR) (time frame: Up to 24 Months). 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 NCT04906096.

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 5 Aug 2026.

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