RECRUITING

Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL

Conditions

Primary Central Nervous System Lymphoma Non-Hodgkin Lymphoma of Extranodal Site

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2021-06-01

Study Completion:2026-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04906096

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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). * 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. * 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	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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).
* 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.
* 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

* 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.
* 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.

Contacts and Locations

Study Contact

Lakshmi Nayak, MD

CONTACT

(617) 632-2166

Lakshmi_Nayak@dfci.harvard.edu

Principal Investigator

Lakshmi Nayak, MD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Brigham and Women's Hospital

Boston, Massachusetts, 02115

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: Lakshmi Nayak, MD

Lakshmi Nayak, MD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-01

Study Completion Date2026-12-01

Study Record Updates

Study Start Date2021-06-01

Study Completion Date2026-12-01

Terms related to this study

Keywords Provided by Researchers

Primary Central Nervous System Lymphoma
Non-Hodgkin Lymphoma of Extranodal Site

Additional Relevant MeSH Terms

Primary Central Nervous System Lymphoma
Non-Hodgkin Lymphoma of Extranodal Site