RECRUITING

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)

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 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.

Official Title

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

Quick Facts

Study Start:2017-12-28
Study Completion:2026-10
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT03328078

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 CriteriaExclusion Criteria
  1. 1. Males and females greater than or equal to 18 years of age
  2. 2. Life expectancy of at least 3 months
  3. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
  4. 4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
  5. 1. Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion \[≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging \[MRI\] or head computed tomography \[CT\] on imaging within 28 days prior to Cycle 1 Day 1\]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
  6. 2. For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1.
  7. 1. Participants with only intraocular PCNSL without brain lesion or CSF involvement, T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS
  8. 2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).
  9. 3. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.
  10. 4. Active malignancy other than PCNSL requiring systemic therapy
  11. 5. Previous BTKi treatment (Part C only).
  12. 6. History of Grade ≥ 3 rhabdomyolysis without complete recovery
  13. 7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
  14. 8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
  15. 9. Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only).
  16. 10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)
  17. 11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.
  1. Pregnancy or breastfeeding
  2. Severe psychiatric disorders
  3. Active substance abuse
  4. Unstable medical conditions
  5. Inability to comply with study requirements

Contacts and Locations

Study Contact

Catherine Wang, MD
CONTACT
617-503-6500
clinicaltrials@curis.com

Study Locations (Sites)

St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
United States
Mayo Clinic
Phoenix, Arizona, 85054
United States
City of Hope
Duarte, California, 91010
United States
Providence St. John's Health Center
Santa Monica, California, 90404
United States
UCLA Department of Medicine - Hematology/Oncology
Santa Monica, California, 90404
United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510
United States
Mayo Clinic
Jacksonville, Florida, 32224
United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611
United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
United States
Mayo Clinic
Rochester, Minnesota, 55905
United States
Fred and Pamela Buffett Cancer Center
Omaha, Nebraska, 68198
United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601
United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
United States
Mt Sinai
New York, New York, 10029
United States
Columbia University Irving Medical Center
New York, New York, 10032
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, 27710
United States
Cleveland Clinic
Cleveland, Ohio, 44195
United States
Providence Neurological Specialties West
Portland, Oregon, 97225
United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
United States
UPMC Hilman Cancer Center
Pittsburgh, Pennsylvania, 15232
United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
United States
UT Southwestern Medical Center
Dallas, Texas, 75235
United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
United States
Swedish Cancer Institute
Seattle, Washington, 98104
United States
University of Washington Medical Center
Seattle, Washington, 98195
United States

Collaborators and Investigators

Sponsor: Curis, Inc.

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 Date2017-12-28
Study Completion Date2026-10

Study Record Updates

Study Start Date2017-12-28
Study Completion Date2026-10

Terms related to this study

Keywords Provided by Researchers

  • MYD88
  • IRAK4
  • NHL
  • PCNSL
  • Lymphoma
  • Neoplasms
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Lymphoma, Non-Hodgkin
  • Relapsed/refractory Central Nervous System (CNS) Lymphoma
  • Systemic Lymphoma with Concurrent CNS Lymphoma
  • Systemic Lymphoma with a History of Treated CNS Lymphoma
  • Ibrutinib
  • Bruton's tyrosine kinase (BTKi)
  • Primary CNS Lymphoma

Additional Relevant MeSH Terms

  • Relapsed Hematologic Malignancy
  • Refractory Hematologic Malignancy
  • Relapsed Primary Central Nervous System Lymphoma
  • Refractory Primary Central Nervous System Lymphoma