A study of oral asciminib versus other TKIs in adult patients with newly diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase
- Conditions
- Health Condition 1: C921- Chronic myeloid leukemia, BCR/ABL-positive
- Registration Number
- CTRI/2021/12/038740
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Patients with CML-CP within 3 months of diagnosis.
-Diagnosis of CML-CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations (presence of BCR-ABL1 in a review of a minimum 20 metaphases is required). Documented chronic phase CML will meet all the below criteria :
< 15% blasts in peripheral blood and bone marrow,
< 30% blasts plus promyelocytes in peripheral blood and bone marrow,
< 20% basophils in the peripheral blood,
Platelet (PLT) count >= 100 x 109/L (>= 100,000/mm3),
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
-Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1.
-Adequate end organ function as defined by:
Total bilirubin (TBL) < 3 x upper limit of normal (ULN); patients with Gilbertâ??s syndrome may only be included if TBL <= 3.0 x ULN or direct bilirubin <= 1.5 x ULN
Creatinine clearance (ClCr) >= 30 mL/min as calculated using Cockcroft-Gault formula
Serum lipase <= 1.5 x ULN. For serum lipase > ULN - <= 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis
-Patients must have the following laboratory values >= lower limit of normal (LLN) or corrected to within normal limits with supplements prior to randomization:
--Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with ClCr >= 90 mL/min)
--Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with ClCr >= 90 mL/min)
--Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with ClCr >= 90 mL/min)
--For patients with mild to moderate renal impairment (ClCr >= 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be >= LLN or corrected to within normal limits with supplements prior to randomization.
o ClCr as calculated using Cockcroft-Gault formula
-Signed informed consent must be obtained prior to any study related screening procedures being performed
-Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which is amenable to standardized Real time quantitative polymerase chain reaction (RQ-PCR) quantification.
-Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with imatinib for <=2 weeks is allowed, but no other treatment with tyrosine kinase inhibitors prior to study entry is permitted
-Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required)
-Impaired cardiac function or cardiac repolarization abnormality
-Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia)
-History of significant congenital or acquired bleeding disorder unrelated to cancer. 6. Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery
-History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
-History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis
-History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease
-Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab/anti HBc) will be performed at screening. A patient having positive HBV-DNA should not be enrolled in the study.
-History of Human Immunodeficiency Virus (HIV) unless well-controlled on a stable dose of anti-retroviral therapy at the time of screening
-Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
-Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
-If local regulations deviate from the contraception methods listed
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Major Molecular response (MMR) at Week 48Timepoint: Week 48
- Secondary Outcome Measures
Name Time Method Major Molecular response (MMR) at Week 96Timepoint: Week 96