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Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)

Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia, Myeloid, Chronic Phase

Intervention: Imatinib mesylate (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

Summary

This study investigated the safety and efficacy of 400mg Versus 800mg imatinib in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints.

Clinical Details

Official title: A Randomized Open-label Study of 400 mg Versus 800 mg of Imatinib Mesylate in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months

Secondary outcome:

Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months

Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months

Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months

Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts

Time to First Major Molecular Response

Time to First Complete Cytogenetic Response

Time to First Complete Hematological Response (CHR)]

Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms

Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms

Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms

Estimated Rate of Overall Survival (OS) in Two Treatment Arms

Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss

Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)

Mean Actual Dose Intensity Per Day

Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12

Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)

Time to First Complete Molecular Response (CMR)]

Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients within 6 months of diagnosis (date of initial diagnosis is the date of first

cytogenetic analysis)

- Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic

confirmation of Philadelphia chromosome of (9;22) translocations and presence of Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl)

- Documented chronic phase CML

- Adequate end organ function as defined by:

- total bilirubin < 1. 5 x Upper Limit of Normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate

transaminase (SGPT) < 2. 5 x ULN

- creatinine < 1. 5 x ULN

Exclusion Criteria:

- Patients in late chronic phase, accelerated phase, or blastic phase are excluded

- Patients who have received other investigational agents

- Patients who received Gleevec/Glivec for any duration prior to study entry, with the

exception of those patients successfully completing [CSTI571A2107 (NCT00428909)] study immediately prior to the participation in this study

- Patient received any treatment for CML prior to study entry for longer than 2 weeks

with the exception of hydroxyurea and/or anagrelide

- Patients with another primary malignancy except if the other primary malignancy is

neither currently clinically significant or requiring active intervention

- Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential

without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).

- Patient with a severe or uncontrolled medical condition (i. e., uncontrolled

diabetes,chronic renal disease)

- Patient previously received radiotherapy to ≥ 25% of the bone marrow

- Patient had major surgery within 4 weeks prior to study entry, or who have not

recovered from prior major surgery

- Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥

3

- Patients with International normalized ratio (INR) or partial thromboplastin time

(PTT) > 1. 5 x ULN, with the exception of patients on treatment with oral anticoagulants

- Patients with known positivity for human immunodeficiency virus (HIV); baseline

testing for HIV is not required

- Patients with identified sibling donors where allogeneic bone marrow transplant is

elected as first line treatment Other protocol-defined inclusion/exclusion criteria applied.

Locations and Contacts

Novartis Investigative Site, Buenos Aires, Argentina

Novartis Investigative Site, La Plata, Argentina

Novartis Investigative Site, South Brisbane, Australia

Novartis Investigative Site, Campinas, Brazil

Novartis Investigative Site, Calgary, Canada

Novartis Investigative Site, Montreal, Canada

Novartis Investigative Site, Ottawa, Canada

Novartis Investigative Site, Quebec, Canada

Novartis Investigative Site, Bologna, Italy

Novartis Investigative Site, Firenze, Italy

Novartis Investigative Site, Milano, Italy

Novartis Investigative Site, Napoli, Italy

Novartis Investigative Site, Orbassano, Italy

Novartis Investigative Site, Roma, Italy

University of South Alabama, Mobile, Alabama 36693, United States

Alta Bates Comprehsenive Cancer Center, Berkeley, California 94704, United States

University of Miami, Berkeley, California 94704, United States

South Bay Oncology Hematology Partners, Campbell, California 95008, United States

UCLA Medical Center, Los Angeles, California 90095, United States

Rocky Mountain Cancer Center, Denver, Colorado 80218, United States

Osler Medical Inc., Melbourne, Florida 32901, United States

Advanced Medical Specialists, Miami, Florida 33176, United States

Integrated Community Oncology Network, Orange Park, Florida 32073, United States

Hematology-Oncology Associates, P.A., Pensacola, Florida 32501, United States

Palm Beach Cancer Institute, West Palm Beach, Florida 233401, United States

Palm Beach Cancer Institute, West Palm Beach, Florida 33401, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Indiana Blood and Marrow Institutw, Beech Grove, Indiana 46107, United States

Indiana Blood and Marrow Transplant, Beech Grove, Indiana 46107, United States

University of Iowa Hospitals & Clinic, Iowa City, Iowa 52242, United States

University of Kentucky, Lexington, Kentucky 40536, United States

University of Kentucky - C201 Clinic, Lexington, Kentucky 40536, United States

Lousville Oncology, Clinical Research Program M-25, Louisville, Kentucky 40202, United States

Jayne S. Gurtler, MD, Laura A. Brinz, MD & Angelo Russo, MD, Metairie, Louisiana 70006, United States

Hematology and Oncology Specialists, New Orleans, Louisiana 70115, United States

LSU Health Science Center, Shreveport, Louisiana 71103, United States

LSU Health Scine Center, Shreveport, Louisiana 71130, United States

St. Agnes Hospital, Baltimore, Maryland 21229, United States

Great Lakes Cancer Institute, Lansing, Michigan 48910, United States

U of Minnesota, Minneapolis, Minnesota 55455, United States

University of Minnesota, Minneapolis, Minnesota 55455, United States

Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

San Juan Oncology Associates, Farmington, New Mexico 87401, United States

Novartis Investigative Site, St. Leonards, New South Wales, Australia

Novartis Investigative Site, Waratah, New South Wales, Australia

Novartis Investigative Site, Westmead, New South Wales, Australia

Roswell Park Cancer Institute, Buffalo, New York 14263, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

Cancer Center of the Carolinas, Greenville, North Carolina 29615, United States

Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, United States

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

University Hospitals of Cleveland, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, United States

Kaiser Permanente Northwest Region, Portland, Oregon 97227, United States

Kaiser Permanente Northwest Region Oncology/Hemacology, Portland, Oregon 97227, United States

University of Pittsburg, Hillman Cancer Center, Pittsburgh, Pennsylvania 15232, United States

Western Pennsylvania Hospital, Pittsburgh, Pennsylvania 15224, United States

Novartis Investigative Site, Herston, Queensland, Australia

Novartis Investigative Site, Woolloongabba, Queensland, Australia

Novartis Investigative Site, Adelaide, South Australia, Australia

MUSC Hollings Cancer Center, Charleston, South Carolina 29425, United States

Cancer Center of the Carolinas, Greenville, South Carolina 29615, United States

Cancer Centers of the Carolinas, Greenville, South Carolina 29615, United States

The Jones Clinic, Germantown, Tennessee 38138, United States

Sarah Cannon Research Institute, Nashville, Tennessee 37203, United States

UT Southwestern Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas 75390, United States

MD Anderson Cancer Center, Houston, Texas 77030, United States

University of Texas / MD Anderson Cancer Center, Houston, Texas 77030-4009, United States

Novartis Investigative Site, East Melbourne, Victoria, Australia

Novartis Investigative Site, Fitzroy, Victoria, Australia

Novartis Investigative Site, Frankston, Victoria, Australia

Novartis Investigative Site, Parkville, Victoria, Australia

Novartis Investigative Site, Prahran, Victoria, Australia

University of Virgina Cancer Center, UVA Division of Hematology & Oncology, Charlottesville, Virginia 22908, United States

Additional Information

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Starting date: June 2005
Last updated: January 5, 2012

Page last updated: August 23, 2015

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