AzTrials
AzTrials

Relapsed Hematologic MalignancyPhase 1/2NCT03328078

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)

A Phase 1/2 study testing Emavusertib and Ibrutinib in people with Relapsed Hematologic Malignancy and Refractory Hematologic Malignancy, run by Curis, Inc. at 45 sites in 7 countries.

Recruiting

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

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Emavusertib and Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
152 participants
Where
45 sitesin 7 countries
Study dates
28 Dec 2017to Oct 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

  • Males and females greater than or equal to 18 years of age
  • Life expectancy of at least 3 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
  • Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
  • 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.
  • 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.

Who cannot join

  • 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
  • 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).
  • 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.
  • Active malignancy other than PCNSL requiring systemic therapy
  • Previous BTKi treatment (Part C only).
  • History of Grade ≥ 3 rhabdomyolysis without complete recovery
Show all 12Show fewer
  • Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
  • Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
  • 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).
  • Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval
  • 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)
  • Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.

Trial locations and contacts

45 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

Ahmed Hamdy, MD contact

617-503-6500

clinicaltrials@curis.com

45 sites in 7 countries

United States27 sites, 18 recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Recruiting

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

    Recruiting

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Recruiting

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

    Active, not recruiting

  • City of Hope

    Duarte, California, 91010

    Recruiting

  • Duke University Medical Center, Duke Cancer Center

    Durham, North Carolina, 27710

    Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Completed

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Mayo Clinic

    Jacksonville, Florida, 32224

    Recruiting

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

    Completed

  • Smilow Cancer Hospital at Yale-New Haven

    New Haven, Connecticut, 06510

    Completed

  • Mt Sinai

    New York, New York, 10029

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Withdrawn

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Recruiting

  • Fred and Pamela Buffett Cancer Center

    Omaha, Nebraska, 68198

    Recruiting

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Completed

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

    Recruiting

  • Mayo Clinic

    Phoenix, Arizona, 85054

    Completed

  • UPMC Hilman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Recruiting

  • Providence Neurological Specialties West

    Portland, Oregon, 97225

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Recruiting

  • Huntsman Cancer Institute, University of Utah

    Salt Lake City, Utah, 84112

    Recruiting

  • Providence St. John's Health Center

    Santa Monica, California, 90404

    Recruiting

  • UCLA Department of Medicine - Hematology/Oncology

    Santa Monica, California, 90404

    Withdrawn

  • Swedish Cancer Institute

    Seattle, Washington, 98104

    Completed

  • University of Washington Medical Center

    Seattle, Washington, 98195

    Recruiting

Other trials in United States

France4 sites, 4 recruiting

  • Institut Bergonie

    Bordeaux

    Recruiting

  • Hopital de la Timone

    Marseille

    Recruiting

  • Hospital Pitie Salpetriere

    Paris

    Recruiting

  • Institut Curie Hospital

    Paris

    Recruiting

Other trials in France

Italy4 sites, 4 recruiting

  • Università di Torino Croce e Carle

    Cuneo

    Recruiting

  • SODc Ematologia Azienda Ospedaliera Universitaria Careggi

    Florence

    Recruiting

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

    Meldola

    Recruiting

  • IRCCS San Raffaele Scientific Institute

    Milan

    Recruiting

Other trials in Italy

Israel3 sites, 3 recruiting

  • Hematology Department Soroka UMC / Heanatology Department

    Beersheba

    Recruiting

  • Rambam Medical Center

    Haifa

    Recruiting

  • Hadassah Medical Center / Ein-Carem

    Jerusalem

    Recruiting

Other trials in Israel

Poland3 sites, 2 recruiting

  • Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz

    Gdansk

    Recruiting

  • Oddzial Kliniczny Hematologii

    Krakow

    Withdrawn

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

    Warsaw

    Recruiting

Other trials in Poland

Spain3 sites, 3 recruiting

  • University Hospital Vall d'Hebron

    Barcelona

    Recruiting

  • MD Anderson Cancer Center Madrid

    Madrid

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville

    Recruiting

Other trials in Spain

Czechia1 site, 1 recruiting

  • Všeobecná fakultní nemocnice v Praze

    Prague

    Recruiting

Other trials in Czechia

About this study

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

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).

Read more

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.

Being tested
Emavusertib, Ibrutinib
Keywords
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 tyrosine kinase inhibitor (BTKi), Primary CNS Lymphoma
Medical subject headings
Hematologic Neoplasms, Lymphoma, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin

What participants receive

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

  • EmavusertibDrug

    Also called CA-4948

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

  • IbrutinibDrug

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

Study groups in NCT03328078
Study groupRoleWhat they receive
Emavusertib (CA-4948) dose escalationExperimentalPart A1: Dose-level cohorts with up to approximately 6 participants each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.
Receives: Drug: Emavusertib
Emavusertib (CA-4948) and ibrutinib dose escalationExperimentalPart A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg QD or 420 mg QD of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg BID. It is anticipated that 12 to 20 participants at a potential dose level will be required to establish optimal combination dosing.
Receives: Drug: Emavusertib; Drug: Ibrutinib
Emavusertib (CA-4948) and ibrutinib dose expansionExperimentalIn two Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in participants with R/R PCNSL who have progressed on a BTKi. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. In Cohort 2, emavusertib 200 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles.
Receives: Drug: Emavusertib; Drug: Ibrutinib
Emavusertib (CA-4948) and ibrutinibExperimentalIn this part of the study (Part C), eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will receive 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. Treatments will be administered continuously in 28-day treatment cycles.
Receives: Drug: Emavusertib; Drug: Ibrutinib

What is being measured

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

  1. Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT)

    The number of participants with a dose-limiting toxicity (DLT) in the first treatment cycle

    Measured: 12 months

  2. Part A: Maximum tolerated dose (MTD) of emavusertib as a monotherapy and in combination with ibrutinib measured by dose-limiting toxicities (DLTs)

    MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (<33%) experience a dose limiting toxicity.

    Measured: 12 months

  3. Part A: Recommended Phase 2 Dose (RP2D) of emavusertib as a monotherapy and in combination with ibrutinib based on overall tolerability data

    RP2D selected based on overall tolerability data from all participants treated at different dose levels and will not exceed the MTD.

    Measured: 12 months

  4. Part B: Overall Response Rate (ORR) in participants with R/R PCNSL

    Measured: 18 months

  5. Part C: ORR in participants with R/R PCNSL

    Measured: 18 months

Secondary outcomes (11)

  1. Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by AUC

    Area Under the concentration-time curve (AUC)

    Measured: 24- 66 months

  2. Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmax

    Maximum plasma concentration (Cmax)

    Measured: 24- 66 months

  3. Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmin

    Minimum plasma concentration (Cmin)

    Measured: 24- 66 months

  4. Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Tmax

    Time to maximum plasma concentration (Tmax)

    Measured: 24- 66 months

  5. Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by plasma terminal half-life

    Plasma terminal elimination half-life (T 1/2)

    Measured: 24- 66 months

  6. Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by ORR

    Assessed by ORR

    Measured: 24- 36 months

  7. Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by duration of response (DOR)

    Assessed by DOR

    Measured: 24- 66 months

  8. Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by disease control rate (DCR)

    Assessed by DCR

    Measured: 24- 36 months

  9. Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by progression free survival (PFS)

    Assessed by PFS

    Measured: 24- 66 months

  10. Parts A, B and C: To assess efficacy of emavusertib as a monotherapy, in combination with ibrutinib and ibrutinib as monotherapy measured by overall survival (OS)

    Assessed by OS

    Measured: 24 - 66 months

  11. Parts B and C: To assess the safety and tolerability of emavusertib as monotherapy, ibrutinib as monotherapy and emavusertib in combination with ibrutinib in participants with R/R PCNSL

    Measured by the number of participants with treatment-emergent adverse events (TEAEs) and treatment-related adverse events

    Measured: up to 66 months

Timeline

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

  1. First posted1 Nov 2017
  2. Study start28 Dec 2017
  3. Primary completionJul 2027 (estimated)
  4. Study completionOct 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
Sequential
Model description
Part A will evaluate escalating doses of emavusertib (CA-4948) either as monotherapy (Part A1) or in combination with ibrutinib (Part A2). Enrollment is closed for Part A1 and A2. Part B will comprise two expansion cohorts to assess efficacy and safety of emavusertib in combination with ibrutinib in R/R PCNSL. Part C will comprise three cohorts 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.
Masking
None (open label)
Enrolment
152 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03328078
Sponsor's protocol ID
CA-4948-101
Other IDs
2024-513312-95-00, 2022-000891-20
Status last verified
Oct 2026
First submitted
17 Oct 2017
Last updated
6 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Emavusertib and Ibrutinib in people with Relapsed Hematologic Malignancy and Refractory Hematologic Malignancy, run by Curis, Inc. at 45 sites in 7 countries.

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 6 inclusion and 12 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 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, France, Italy, Israel, Poland and 2 more countries. 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?

Contact Ahmed Hamdy, MD (617-503-6500, clinicaltrials@curis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT) (time frame: 12 months). The study lists 5 primary outcomes in all. 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 NCT03328078.

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 6 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in