A study to evaluate the safety and efficacy of KRT-232 in combination with Acalabrutinib in patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia.
- Conditions
- - Relapsed/Refractory (R/R) de novo or transformed TP53 ABC (non-GCB) or GCB diffuse large B-cell lymphoma (DLBCL)- R/R TP53 chronic lymphocytic leukemia (CLL) naïve to prior Bruton's tyrosine kinase (BTK) inhibitor or small lymphocytic lymphoma (SLL)- R/R DLBCL with non-germinal center B-cell like(GCB) subtype- R/R DLBCL with double-expressor lymphoma subtypeMedDRA version: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10012821Term: Diffuse large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10003908Term: B-cell small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002464-31-PT
- Lead Sponsor
- Kartos Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 85
1. Adults =18 years of age;
2. Patient population:
Cohort 1 (R/R DLBCL):
a) Histologically confirmed diagnosis of de novo or transformed TP53^wt ABC (non-GCB) or GCB DLBCL based on 2016 WHO Classification;
i) Phase 2: 25 or more subjects with non-GCB and 10 or more subjects with double-expressor lymphoma will be enrolled as described in Section 10.2 of the study protocol;
b) R/R DLBCL which has been treated with at least 2 prior lines of systemic therapy or at least 1 prior line of systemic therapy in subjects who are ineligible for hematopoietic stem cell transplantation (autologous or allogeneic) for reasons other than active disease;
c) At least 1 measurable site of disease on computed tomography (CT) (defined as >1.5 cm in longest transverse diameter of a lesion [LDi]) and clearly measurable in 2 perpendicular dimensions);
Cohort 2 (R/R CLL/SLL):
d) Histologically confirmed diagnosis of TP53^wt CLL/SLL according to iwCLL criteria;
e) Previously treated with at least 1 prior regimen according to
current guidelines;
f) Active disease meeting at least 1 of the iwCLL 2008 criteria for
requiring treatment;
3. ECOG performance status of 0 to 2;
4. Adequate hematologic function within 7 days (Phase 1b) or 28 days (Phase 2) prior to first dose, independent of growth factor support for at least 7 days with the exception of pegylated G-CSF which requires at least 14 days, defined as:
a) Absolute neutrophil count (ANC) =1,000/mm^3;
b) Platelet count =50,000/mm^3;
5. Adequate hepatic function within 7 days (Phase 1b) or 28 days (Phase 2) prior to first dose defined as:
a) Total bilirubin = 2.0 x upper limit of normal (ULN). Subjects with known Gilbert's syndrome or disease-related hemolysis must have a total bilirubin =3.0 X ULN;
b) Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) =2.5 ULN;
6. Adequate renal function within 7 days (Phase 1b) or 28 days (Phase 2) prior to the first dose defined as an estimated creatinine clearance =30 mL/min by Cockcroft Gault;
7. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential must both use a highly effective contraception method during the study. In addition, after the last dose of study drug, female subjects must continue to use a highly effective method of contraception for 1 month and 1 week and male subjects must continue to use a highly effective method of contraception for 3 months and 1 week. A woman is considered of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal) unless permanently sterile.
Note: Marketed drugs administered concomitantly in this study may have different contraception requirements, including required duration of contraception use. The contraception requirements in the local prescribing guidelines must be followed for all concomitant drugs administered in this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 51
1. Subjects with a history of CNS involvement;
2. Any recent prior therapy meeting one or more of the following criter:
a) Concurrent anticancer treatment, such as chemotherapy, cytoreductive therapy, immune therapy, or cytokine therapy:
i) DLBCL: Within 14 days prior to the first dose of study treatment;
ii) CLL/SLL: Within 28 days prior to the first dose of study treatment;
b) Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within 3 months prior to the first dose of study treatment;
c) Subjects who have received immunosuppressive therapy for graft-versus-host disease within 6 months prior to first dose of study treatment;
3. Subjects previously treated with MDM2 antagonist therapies;
4. Subjects previously treated with a BTK inhibitor;
5. Subjects with a history of bleeding diathesis or major hemorrhage within 6 months prior to first dose of study treatment;
6. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug;
7. Participation in another interventional clinical study within the past 4 weeks of the first dose of study treatment (participation in observational studies is permitted)
8. Uncontrolled intercurrent illness including but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure, unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements;
9. Grade 2 or higher QTc prolongation (>480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]);
10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach; or extensive small bowel resection that is likely to affect absorption; symptomatic inflammatory bowel disease, or partial or complete bowel obstruction; or gastric restrictions and bariatric surgery, such as gastric bypass or difficulty swallowing which may hamper compliance with study treatment
11. Subjects with uncontrolled bacterial, fungal, parasitic, or viral infection. Subjects with acute bacterial infections requiring antibiotic use should not enroll until the infection is stable in the judgement of the treating physician; these subjects may be on antibiotics at time of enrollment;
12.Subjects with active fever (temperature higher than 38.2°C [100.8°F]) within 14 days prior to the first dose of study treatment
13. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV);
14. Known history of HIV;
15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, preprohormone) within 7 days of first dose of study drug;
16. Phase 1 only: Requires treatment with a strong and/or moderate CYP3A inhibitor/inducer within 7 days prior to first dose of study drug;
17. Phase 2 only: Requires treatment with a strong CYP3A inhibitor/inducer within 7 days prior to first dose of study drug;
18. Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study provided the proton pump inhibitor is discontinued at least 5 days prior to first dose of study drug;
19. Other malign
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method