RecruitingPhase 1Phase 2NCT03328078

CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL)

An Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma


Sponsor

Curis, Inc.

Enrollment

152 participants

Start Date

Dec 28, 2017

Study Type

INTERVENTIONAL

Conditions

Summary

This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies. This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete). Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles. Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new drug called emavusertib (CA-4948) — which blocks a signalling protein called IRAK4 — in patients with primary central nervous system lymphoma (PCNSL), a type of lymphoma that occurs in the brain and spinal cord, that has come back or stopped responding to prior treatment. **You may be eligible if...** - You are 18 or older - You have confirmed PCNSL that has returned or not responded to at least one prior treatment - You are well enough to participate (ECOG performance status 0, 1, or 2) - Your life expectancy is at least 3 months - Your organ function meets the study requirements **You may NOT be eligible if...** - You have never been treated for PCNSL before - Your organ function is too poor - You have serious heart problems or uncontrolled infections - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGEmavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

DRUGIbrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.


Locations(45)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Mayo Clinic

Phoenix, Arizona, United States

City of Hope

Duarte, California, United States

Providence St. John's Health Center

Santa Monica, California, United States

UCLA Department of Medicine - Hematology/Oncology

Santa Monica, California, United States

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States

Mayo Clinic

Jacksonville, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Fred and Pamela Buffett Cancer Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Mt Sinai

New York, New York, United States

Columbia University Irving Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center, Duke Cancer Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Providence Neurological Specialties West

Portland, Oregon, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

UPMC Hilman Cancer Center

Pittsburgh, Pennsylvania, United States

University of Tennessee Medical Center

Knoxville, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Swedish Cancer Institute

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Všeobecná fakultní nemocnice v Praze

Prague, Czechia

Institut Bergonie

Bordeaux, France

Hopital de la Timone

Marseille, France

Hospital Pitie Salpetriere

Paris, France

Institut Curie Hospital

Paris, France

Hematology Department Soroka UMC / Heanatology Department

Beersheba, Israel

Rambam Medical Center

Haifa, Israel

Hadassah Medical Center / Ein-Carem

Jerusalem, Israel

Università di Torino Croce e Carle

Cuneo, Italy

SODc Ematologia Azienda Ospedaliera Universitaria Careggi

Florence, Italy

IRST - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

IRCCS San Raffaele Scientific Institute

Milan, Italy

Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz

Gdansk, Poland

Oddzial Kliniczny Hematologii

Krakow, Poland

NarodowyInstytutu Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytutu Badawczy

Warsaw, Poland

University Hospital Vall d'Hebron

Barcelona, Spain

MD Anderson Cancer Center Madrid

Madrid, Spain

Hospital Universitario Virgen del Rocio

Seville, Spain

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NCT03328078


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