Myeloproliferative Neoplasms Clinical Trial

A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

Summary

The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ leukemia-cml/" >CML-CP. The Investigator selected TKI will be one of the following treatment options for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.

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Full Description

This study is a phase III, multi-center, open-label, randomized study of oral asciminib 80 mg QD versus Investigator selected TKI (imatinib, nilotinib, dasatinib, or bosutinib) in adult patients with newly diagnosed Ph+ CML-CP. All comparator TKIs will be made available, unless not permitted by local regulations or local Health Authority, or not approved for the treatment of CML in the country.

The study is designed to compare the efficacy of asciminib 80 mg QD with Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the treatment options approved by major Health Authorities for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.

Approximately 402 patients will be randomized in a 1:1 ratio to asciminib and Investigator selected TKI.

Randomization will be stratified based on the following two stratification factors:

ELTS score (low versus intermediate versus high)
Pre-randomization selected TKI (imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib)).

Prior to randomization, the Investigator, in consultation with the patient, considering the current treatment paradigm and patient characteristics and comorbidities, will make a selection of preference for imatinib or 2G TKI (nilotinib or dasatinib or bosutinib) if the patient is randomized to the comparator arm.

To further ensure that the distribution of patients, between imatinib and 2G TKIs (nilotinib or dasatinib or bosutinib), in the Investigator selected TKI arm is reflective of the use of these agents in clinical practice, the enrollment into the strata of imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib) based on the pre-randomization selection of TKI will be managed by Interactive Response Technology to be approximately 50% versus 50%.

Treatment arms: The study will have 2 treatment arms:

Arm 1: asciminib 80 mg QD under fasting conditions
Arm 2: Investigator selected TKI that will include one of the below treatments:
Imatinib 400 mg QD administered with food
Nilotinib 300 mg BID administered under fasting conditions
Dasatinib 100 mg QD administered with or without meal
Bosutinib 400 mg QD administered with food.

No crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed.

Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, or until premature discontinuation due to treatment failure, disease progression or intolerance or due to Investigator or participant decision.

Duration of study: The End of Study will occur 5 years from the last patient first treatment in the study. Patients who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to AP/BC) until the End of Study.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

Male or female patients ≥ 18 years of age.
Participants with CML-CP within 3 months of diagnosis.
Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of Philadelphia chromosome

Documented chronic phase CML will meet all the below criteria (Hochhaus et al 2020):

< 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 count ≥ 100 x 109/L (≥ 100,000/mm3),

No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,or 1. 5. Adequate end organ function as defined by:

Total bilirubin < 3 x ULN; patients with Gilbert's syndrome may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
Creatinine clearance (CrCl) ≥ 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 6. Participants must have the following laboratory values within normal limits 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 CrCl* ≥ 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 CrCl* ≥ 90 mL/min)
Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* ≥ 90 mL/min)
For patients with mild to moderate renal impairment (CrCl* ≥ 30 mL/min and <90 mLmin) - potassium, total calcium (corrected for serum albumin) and magnesium should be ≥ LLN or corrected to within normal limits with supplements prior randomization.

*CrCl as calculated using Cockcroft-Gault formula 7. Ability to provide written informed consent prior to any study related screening procedures being performed.

8. 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.

Exclusion Criteria:

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 either imatinib, or nilotinib, or dasatinib or bosutinib for ≤2 weeks is allowed, but no other treatment with other tyrosine kinase inhibitors prior to randomization 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 including but not limited to any one of the following:

History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
QTc ≥ 450 ms (male patients), ≥460 ms (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.•Inability to determine the QTcF interval
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). Please refer to Section 6.3.1
History of significant congenital or acquired bleeding disorder unrelated to cancer.
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.

Other protocol-defined Inclusion/exclusion criteria will apply.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

402

Study ID:

NCT04971226

Recruitment Status:

Recruiting

Sponsor:

Novartis Pharmaceuticals

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There are 142 Locations for this study

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City of Hope National Medical Center
Duarte California, 91010, United States More Info
Paul Koller
Principal Investigator
UCLA Medical Center
Los Angeles California, 90095, United States More Info
Laura H Yu
Contact
[email protected]
Gary Schiller
Principal Investigator
Rocky Mountain Cancer Centers
Longmont Colorado, 80501, United States More Info
Bobbie Donnachaidh
Contact
[email protected]
David J Andorsky
Principal Investigator
Florida Cancer Specialists Dept of Oncology (2)
Fort Myers Florida, 33901, United States More Info
Melissa Staggs
Contact
727-216-1143
[email protected]
Vijay Patel
Principal Investigator
Florida Cancer Specialists
Fort Myers Florida, 33901, United States More Info
David Langlois
Contact
239-274-9930
[email protected]
Anjan J Patel
Principal Investigator
Florida Cancer Specialists Panhandle
Tallahassee Florida, 32308, United States More Info
Sheila Gagne
Contact
615-329-7482
[email protected]
Pareshkumar Patel
Principal Investigator
Florida Cancer Specialists
West Palm Beach Florida, 33401, United States More Info
Jennifer Demko
Contact
561-366-4149
[email protected]
Shachar Peles
Principal Investigator
University of Chicago
Chicago Illinois, 60637, United States More Info
Anielska Brautigam
Contact
773-702-8582
[email protected]
Richard A. Larson
Principal Investigator
Illinois Cancer Care P.C. IL Cancer Specialists
Peoria Illinois, 61615, United States More Info
Anginique Walker
Contact
847-827-0319
[email protected]
Leonard Klein
Principal Investigator
University of Iowa Hospitals and Clinics Univ of Iowa Hosp & Clinic
Iowa City Iowa, 52242, United States More Info
Contact
319-356-3425
Grerk Sutamtewagul
Principal Investigator
University of Kentucky
Lexington Kentucky, 40536, United States More Info
Contact
859-218-5151
Reinhold Munker
Principal Investigator
University of Massachusetts Medical Center Dept of Oncology
Worcester Massachusetts, 01655, United States More Info
Contact
774-443-7433
Jonathan Gerber
Principal Investigator
University of Michigan Clinical Trials Office
Ann Arbor Michigan, 48109, United States More Info
D Andra Featherstone
Contact
734-647-8925
[email protected]
Moshe Talpaz
Principal Investigator
Wake Forest University Baptist Medical Center Comprehensive Cancer Ctr
Winston-Salem North Carolina, 27157, United States More Info
Contact
336-716-4464
Bayard L. Powell
Principal Investigator
Oncology Hematology Care Inc
Cincinnati Ohio, 45242, United States More Info
Maggie Lair
Contact
[email protected]
Edward R Broun
Principal Investigator
Williamette Cancer Center
Eugene Oregon, 97401, United States More Info
Nichole Fischer
Contact
[email protected]
Luke Fletcher
Principal Investigator
Avera Cancer Avera Cancer Institute
Sioux Falls South Dakota, 57105, United States More Info
Lauren Donelan
Contact
605-322-3291
[email protected]
Roberto Ferro Valdes
Principal Investigator
Chattanooga Oncology and Hematology Associates PC Tennessee Oncology Chattanooga
Chattanooga Tennessee, 37404, United States More Info
Bertrand Marquess Anz
Principal Investigator
Texas Oncology Texas Onc - Amarillo
Dallas Texas, 75246, United States More Info
Tanya Jauch-Worley
Contact
+1 806 358 8654
[email protected]
Praveen Kumar Tumula
Principal Investigator
Texas Oncology-Baylor USO
Dallas Texas, 75246, United States More Info
Julie Morehouse
Contact
[email protected]
Moshe Levy
Principal Investigator
Texas Oncology
Dallas Texas, 75246, United States More Info
Praveen Kumar Tumula
Principal Investigator
Texas Oncology P A Austin
Dallas Texas, 75251, United States More Info
Francisca Fernandez
Contact
512-421-4163
[email protected]
Jason M Melear
Principal Investigator
University of TX MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Allison Pike
Contact
713-745-1936
[email protected]
Ghayas C Issa
Principal Investigator
Lumi Research
Kingwood Texas, 77339, United States More Info
Contact
281-809-0676
Saleha Sajid
Principal Investigator
Texas Oncology Northeast Texas
Tyler Texas, 75702, United States More Info
Karen Wollard
Contact
903-579-9867
[email protected]
Habte Yimer
Principal Investigator
Virginia Cancer Specialists
Gainesville Virginia, 20155, United States More Info
Marcy Sullivan
Contact
[email protected]
Mitul Gandhi
Principal Investigator
Virginia Oncology Associates
Norfolk Virginia, 23502, United States More Info
Tamira Mann
Contact
757-466-8683
[email protected]
Celeste Bremer
Principal Investigator
Novartis Investigative Site
Kingswood New South Wales, 2747, Australia
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Port Macquarie New South Wales, 2444, Australia
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Woolloongabba Queensland, 4102, Australia
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Adelaide South Australia, 5000, Australia
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SouthPort , 4215, Australia
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Linz Upper Austria, 4010, Austria
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Wien , 1090, Austria
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Bruxelles , 1000, Belgium
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Hasselt , 3500, Belgium
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Leuven , 3000, Belgium
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Sofia , 1797, Bulgaria
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Varna , 9010, Bulgaria
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Calgary Alberta, T2N 4, Canada
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Hamilton Ontario, L8V 1, Canada
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Ottawa Ontario, K1H 8, Canada
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Toronto Ontario, M5G 2, Canada
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Hefei Anhui, 23000, China
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Chongqing Chongqing, 40001, China
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Guangzhou Guangdong, 51051, China
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Shenzhen Guangdong, 51803, China
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Zhengzhou Henan, 45000, China
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Wuhan Hubei, 43002, China
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Chifeng Inner Mongolia, 02409, China
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Nanjing Jiangsu, , China
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Nantong Jiangsu, 22600, China
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Suzhou Jiangsu, 21500, China
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Taiyuan Shanxi, 03000, China
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Xian Shanxi, 71006, China
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Chengdu Sichuan, 61004, China
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Tianjin Tianjin, 30002, China
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Hangzhou Zhejiang, 31000, China
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Wenzhou Zhejiang, 32500, China
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Beijing , 10004, China
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Beijing , 10073, China
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Lanzhou , , China
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Shanghai , 20002, China
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Brno Bohunice Czech Republic, 625 0, Czechia
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Hradec Kralove CZE, 500 0, Czechia
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Ostrava Poruba, 708 5, Czechia
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Aarhus , 8000, Denmark
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Copenhagen , DK-21, Denmark
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Roskilde , 4000, Denmark
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Helsinki , FIN 0, Finland
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Turku , 20520, Finland
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Bordeaux , 33076, France
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Lyon Cedex , 69373, France
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Nantes Cedex 1 , 44093, France
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Paris Cedex 10 , 75475, France
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Mannheim Baden-Wuerttemberg, 68305, Germany
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Aachen , 52074, Germany
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Berlin , 13353, Germany
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Frankfurt , 60590, Germany
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Jena , 07740, Germany
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Luebeck , 23538, Germany
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Debrecen , 4032, Hungary
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Kaposvar , 7400, Hungary
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Kecskemet , 6001, Hungary
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Kolkata West Bengal, 70016, India
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Delhi , 110 0, India
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Petah Tikva , , Israel
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Ramat Gan , 52621, Israel
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Tel Aviv , 64239, Israel
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Bologna BO, 40138, Italy
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Milano MI, 20122, Italy
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Reggio Emilia RE, 42123, Italy
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Roma RM, 00161, Italy
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Verona VR, 37126, Italy
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Nagoya Aichi, 453-8, Japan
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Toyoake city Aichi, 470 1, Japan
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Kashiwa Chiba, 277 8, Japan
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Fukuoka city Fukuoka, 812-8, Japan
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Fukushima city Fukushima, 960 1, Japan
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Sapporo city Hokkaido, 060 8, Japan
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Kobe-city Hyogo, 650-0, Japan
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Kurashiki-city Okayama, 710-8, Japan
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Osaka Sayama Osaka, 589 8, Japan
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Suita Osaka, 565 0, Japan
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Sunto Gun Shizuoka, 411 8, Japan
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Shimotsuke Tochigi, 329-0, Japan
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Chuo-city Yamanashi, 409-3, Japan
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Akita , 010-8, Japan
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Osaka , 545-8, Japan
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Yamagata , 990 9, Japan
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Uijeongbu si Gyeonggi Do, 11759, Korea, Republic of
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Seoul Seocho Gu, 06591, Korea, Republic of
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Seoul , 03080, Korea, Republic of
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Seoul , 03722, Korea, Republic of
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Seoul , 06351, Korea, Republic of
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Kuantan Pahang, 25100, Malaysia
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Subang Jaya Selangor, 47500, Malaysia
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Pulau Pinang , 10990, Malaysia
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Selangor , 68000, Malaysia
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Amsterdam , 1081 , Netherlands
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Bergen , 5021, Norway
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Oslo , 0372, Norway
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Trondheim , 7006, Norway
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Lisboa , 1099 , Portugal
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Porto , 4200-, Portugal
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Vila Nova de Gaia , 4434 , Portugal
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Moscow , 12764, Russian Federation
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Saint Petersburg , 19102, Russian Federation
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Singapore , 11922, Singapore
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Singapore , 16960, Singapore
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Bratislava Slovak Republic, 83310, Slovakia
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Kosice Slovak Republic, 040 6, Slovakia
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Granada Andalucia, 18014, Spain
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Badalona Catalunya, 08916, Spain
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Barcelona Catalunya, 08036, Spain
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El Palmar Murcia, 30120, Spain
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Pamplona Navarra, 31008, Spain
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Madrid , 28046, Spain
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Goteborg , 413 4, Sweden
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Lund , 221 8, Sweden
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Stockholm , 141 8, Sweden
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Bellinzona , 6850, Switzerland
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Zürich , 8091, Switzerland
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Kaohsiung City , 83301, Taiwan
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Taichung , 40447, Taiwan
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London , W12 0, United Kingdom
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Nottingham , NG5, United Kingdom
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Oxford , OX3 7, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 3

Estimated Enrollment:

402

Study ID:

NCT04971226

Recruitment Status:

Recruiting

Sponsor:


Novartis Pharmaceuticals

How clear is this clinincal trial information?

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