Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
Curis, Inc. (Voir sur ClinicalTrials)
décembre 2017
août 2026
19 novembre 2024
This is a multi-center, open-label trial to evaluate the safety, pharmacokinetics (PK),
and anti-cancer activity of oral administration of emavusertib (CA-4948) in adult
patients with relapsed or refractory (R/R) hematologic malignancies. This trial will be
completed in two 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 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
patients with primary central nervous system lymphoma (PCNSL).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/06/2024 14:01:16 | Contact (sur clinicalTrials) | |||
| CLCC RENE HUGUENIN INSTITUT CURIE | 04/12/2024 12:44:01 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Hopital de la Timone - Marseille - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie - Bordeaux - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. Males and females greater than or equal to 18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable).
Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
1. Patients with parenchymal lesions must have unequivocal evidence (e.g.,
presence of at least 1 bi-dimensionally measurable target lesion on brain
magnetic resonance imaging (MRI) or head CT or a new lesion with CSF
involvement) of disease progression on imaging within 28 days prior to Cycle 1
Day 1.
2. For patients with leptomeningeal disease only, CSF cytology must document
lymphoma cells or monotypic cells on flowcytometry, and/or imaging findings
consistent with CSF disease within 28 days prior to Cycle 1 Day 1 (at the
discretion of the Investigator).
Exclusion Criteria for Part B - PCNSL Expansion Cohorts of Combination Therapy
1. Patients with only intraocular PCNSL without brain lesion or CSF involvement or
T-cell lymphoma or systemic presence of lymphoma, or non-CNS lymphoma metastatic to
the CNS
2. 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 patient has been free of the disease for ≥
3 years.
3. Active malignancy other than PCNSL requiring systemic therapy
4. History of Grade ≥ 3 rhabdomyolysis without complete recovery
5. Patient has received external beam radiation therapy to the CNS within 28 days prior
to Cycle 1 Day 1.
6. 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 C1D1; or clinically significant
graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive
medications prior to Screening 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
7. 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, which may be continued as part of
this study without interruption)
8. Prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any
excipients.
1. Males and females greater than or equal to 18 years of age
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable).
Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
1. Patients with parenchymal lesions must have unequivocal evidence (e.g.,
presence of at least 1 bi-dimensionally measurable target lesion on brain
magnetic resonance imaging (MRI) or head CT or a new lesion with CSF
involvement) of disease progression on imaging within 28 days prior to Cycle 1
Day 1.
2. For patients with leptomeningeal disease only, CSF cytology must document
lymphoma cells or monotypic cells on flowcytometry, and/or imaging findings
consistent with CSF disease within 28 days prior to Cycle 1 Day 1 (at the
discretion of the Investigator).
Exclusion Criteria for Part B - PCNSL Expansion Cohorts of Combination Therapy
1. Patients with only intraocular PCNSL without brain lesion or CSF involvement or
T-cell lymphoma or systemic presence of lymphoma, or non-CNS lymphoma metastatic to
the CNS
2. 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 patient has been free of the disease for ≥
3 years.
3. Active malignancy other than PCNSL requiring systemic therapy
4. History of Grade ≥ 3 rhabdomyolysis without complete recovery
5. Patient has received external beam radiation therapy to the CNS within 28 days prior
to Cycle 1 Day 1.
6. 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 C1D1; or clinically significant
graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive
medications prior to Screening 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
7. 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, which may be continued as part of
this study without interruption)
8. Prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any
excipients.