Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasms

Rare Diseases

Syndrome

Anemia

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Single-arm design. all patients are treated with IMP

Patients will be treated orally with CA-4948 at 300 mg BID (2x200mg) over 4 cycles. One cycle consists of 28 days, 21 of which are treatment days, followed by 7 days off.

Patients with erythroid response (HI-E) after 4 cycles who tolerate CA-4948 may continue to receive CA-4948 until loss of HI-E response.

CA-4948

Uwe Platzbecker, Prof. Dr.

Anemia in non-transfusion dependent (NTD) or transfusion dependent (low or high transfusion burden, LTB/HTB) patients with very low, low or intermediate risk myelodysplastic syndromes

Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes With CA-4948

A Phase II, Open-Label, Multicenter Study of Orally Administered CA-4948 for the Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS)

To evaluate the proportion of patients who have an erythroid response (HI-E) according to the modified IWG 2018 criteria separately for both independent substudies.

To evaluate HI-E response from the first day of response until loss of response.

To evaluate the time between start of treatment and first day of response.

To evaluate frequency of red blood cell transfusions in transfusion dependent patients

Neutrophil (HI-N) responses according to IWG 2018 criteria

Platelet (HI-P) responses according to IWG 2018 criteria

Assessments will include characterization of toxicities; characterization of AEs including type, incidence, severity, seriousness, and relationship to treatment

To ensure patient safety, close monitoring is carried and includes the analysis of: transaminases, bilirubin, amylase, lipase, troponin, lactate dehydrogenase, creatine kinase, uric acid, TSH, FT4, urine analysis.

To assess patient-reported quality of life during CA-4948 treatment: 30 questions assessing the quality of life of oncology patients across 10 subscales will be analyzed. All subscales have a score range from 0 to 100 points.

Function subscales: a higher score represents a higher quality of life. Symptoms subscales: higher score represents higher level of symptoms/problems, i.e., represents lower quality of life.

To assess patient-reported quality of life during CA-4948 treatment: 12 items, with four response categories for each item (coded with values from 1 to 4) will be analyzed. FA12 scores are transformed to the range 0-100: Higher levels indicate greater degrees of fatigue.

Curis, Inc.

University of Leipzig

Prof. Dr.

Immune System Diseases

Lymphoma

Hematologic Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Primary Central Nervous System Lymphoma

All Drugs and Chemicals

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Part A1: Dose-level cohorts with up to approximately 6 patients each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.

Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg daily (QD) of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg twice a day (BID). It is anticipated that 12 to 20 patients at a potential dose level will be required to establish optimal combination dosing.

In two PCNSL Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in patients with PCNSL. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in a 28-day cycle in approximately 6 to 9 patients. In Cohort 2, CA-4948 200 mg BID will be administered with ibrutinib in at least 9 patients.

Emavusertib (formulated for oral administration for BID dosing)

Emavusertib

ibrutinib

Reinhard von Roemeling, MD

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. Part A will evaluate the safety and tolerability of escalating doses of emavusertib as monotherapy (Part A1), and in combination with ibrutinib. In Protocol Version (v) 1.0 through v6.0, patients with Waldenström macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) were also enrolled at ibrutinib doses of 420 mg (Part A2). Enrollment into Parts A1 and A2 has been closed. 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).

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 and ibrutinib in PCNSL.

A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

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

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

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

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

Area Under the concentration-time curve (AUC)

Time to maximum plasma concentration (Tmax)

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

CNS liquor with be sampled from an Ommaya reservoir or with a spinal puncture about 3 hours after oral dosing of emavusertib. At approximately the same timepoint, a peripheral blood sample will be taken to obtain a plasma sample. The respective emavusertib concentrations will be measured in the liquor and in plasma samples. The liquor vs plasma concentration ratio will provide a rough estimate of the blood-brain barrier (BBB) penetration of emavusertib following oral dosing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes With CA-4948	NCT05178342	Myelodysplastic... Anemia	CA-4948	18 Years -	University of Leipzig
Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes With CA-4948	NCT05178342	Myelodysplastic... Anemia	CA-4948	18 Years -	University of Leipzig
A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma	NCT03328078	Relapsed Hemato... Refractory Hema... Relapsed Primar... Refractory Prim...	Emavusertib ibrutinib	18 Years -	Curis, Inc.

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Spots Global Cancer Trial Database for irak4

Every month we try and update this database with for irak4 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for irak4 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.