Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Brief summary
To learn if the combination of LOXO-305 (pirtobrutinib) and venetoclax can help to control previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Detailed description
Primary Objective: I. To estimate the therapeutic efficacy of pirtobrutinib consolidation in patients who have detectable CLL in peripheral blood after receiving venetoclax for at least 12 cycles. The primary endpoint will be the rate of undetectable MRD (U-MRD4) in the peripheral blood, assessed by NGS at a threshold of 0.01% sensitivity, after 24 cycles of combination therapy. SECONDARY OBJECTIVES: I. Determine the complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate after 6, 12 18 and 24 cycles of combination therapy, in patients who were not in CR/CRi at study initiation and estimate the time to best response with this combination. II. Determine the cumulative rate of blood and bone marrow minimal residual disease undetectable minimal residual disease (MRD) by next generation sequencing (NGS) at thresholds of 0.01% sensitivity (MRD4), 0.001% sensitivity (MRD5) and 0.0001% sensitivity (MRD6). III. Achievement of undetectable MRD at a sensitivity of 0.0001% (MRD6) in the bone marrow in patients who achieve undetectable (U)-MRD6 in peripheral blood. IV. Determine the safety of combined pirtobrutinib and venetoclax. V. Determine the progression-free and overall survival. OUTLINE: Patients receive pirtobrutinib orally (PO) once daily (QD) and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After 24 cycles of combination therapy, patients who achieve U-MRD4 discontinue therapy. Patients who do not achieve U-MRD4 receive pirtobrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, and then every 24 weeks (6 months) for up to 5 years.
Interventions
DRUGPirtobrutinib
Given by PO
DRUGVenetoclax
GIven by PO
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CLL per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria * Received venetoclax for at least 12 cycles, with MRD \> 0.01% detectable in peripheral blood, by Adaptive Biotechnologies NGS assay, within the month prior to study enrollment * Age 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Serum bilirubin =\< 1.5 x upper limit of normal (ULN) or =\< 3 x ULN for patients with Gilbert's disease * Serum creatinine clearance of \>= 30 ml/min (calculated or measured) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3.0 x ULN, unless clearly due to documented disease involvement, in which case ALT and AST =\< 5.0 x ULN * Platelet count of \>= 50,000/ul, with no platelet transfusion in prior 2 weeks * Absolute neutrophil count (ANC) \>= 1000/ul in the absence of growth factor support * Hemoglobin \>= 8 mg/dL * Activated partial thromboplastin time (aPTT) or partial thromboplastin time and prothrombin time (PT) or international normalized ratio (INR) not greater than 1.5 x ULN * Ability to provide informed consent and adhere to the required follow-up * Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use use both a highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc) during the period of therapy and for 6 months after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for \>= 1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of undetectable (U) minimal residual disease (MRD) in the peripheral blood | Up to completion of cycle 24 (each cycle is 28 days) | Assessed by next generation sequencing (NGS) at a threshold of 0.01% sensitivity. The rate of U-MRD will be reported separately for each cohort, along with the corresponding exact 95% confidence interval. |
Countries
United States
Outcome results
None listed