An Extension Study to Determine the Safety and Anti-Leukemic Effects of Imatinib Mesylate in Adult Participants With Ph+ Leukemia

NCT ID: NCT00171249

Last Updated: 2021-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 293 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-08-09
• Study Completion Date: 2013-09-23

Brief Summary

The objectives of Part 1 of the study were:

• To determine the rate of hematologic response (HR) lasting ≥4 weeks in participants with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the accelerated phase (AP).
• To evaluate duration of HR, overall survival, cytogenetic response (CyR), time to blast crisis in CML participants in the AP, improvement of symptomatic parameters, tolerability and safety of STI571 treatment.

The objective of the extension (Part 2) was:

-To enable participants to have access to study drug and continue study treatment and to decrease data collection to include only overall survival and serious adverse events.

Conditions

Philadelphia Positive Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg

Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 400 mg

Intervention Type: DRUG

STI571 capsules and tablets

Lymphoid Blast Crisis 400 mg

Participants with lymphoid blast crisis received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 400 mg

Intervention Type: DRUG

STI571 capsules and tablets

Acute Lymphoblastic Leukemia 400 mg

Participants with acute lymphoblastic leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 400 mg

Intervention Type: DRUG

STI571 capsules and tablets

Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg

Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 600 mg

Intervention Type: DRUG

STI571 capsules and tablets

Lymphoid Blast Crisis 600 mg

Participants with lymphoid blast crisis received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 600 mg

Intervention Type: DRUG

STI571 capsules and tablets

Acute Lymphoblastic Leukemia 600 mg

Participants with acute lymphoblastic leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 600 mg

Intervention Type: DRUG

STI571 capsules and tablets

Acute Myeloid/Myelogenous Leukemia 600 mg

Participants with acute myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first.

Group Type: EXPERIMENTAL

STI571 600 mg

Intervention Type: DRUG

STI571 capsules and tablets

Interventions

STI571 400 mg

STI571 capsules and tablets

Intervention Type: DRUG

STI571 600 mg

STI571 capsules and tablets

Intervention Type: DRUG

Other Intervention Names

Imatinib mesylate; Glivec®; GleevecTM; Imatinib mesylate; Glivec®; GleevecTM

Eligibility Criteria

Inclusion Criteria

• Male or female participants, aged ≥18 years, with a histologically confirmed diagnosis of Ph+ leukemia of one of the following types:

• Accelerated phase chronic myeloid/myelogenous leukemia (CML).
• Acute lymphoid/lymphoblastic leukemia (ALL) or acute myeloid/myelogenous leukemia (AML) in first or subsequent relapse after either standard chemotherapy, autologous or allogeneic bone marrow transplantation, or high-dose treatment with peripheral blood stem cell support, or
• ALL or AML refractory to standard chemotherapy (no complete remission achieved after two courses of conventional induction chemotherapy).
• Lymphoid blastic phase of CML in first or subsequent relapse or refractory to standard chemotherapy.
• With serum serum glutamate oxaloacetate transaminase (aspartate aminotransferase) and serum glutamate pyruvate transaminase (alanine aminotransferase) not more than 3 x upper limit of normal (ULN) (or not more than 5xULN if clinically suspected leukemic involvement of the liver), serum creatinine concentration not more than 2xULN, and total serum bilirubin level not more than 3xULN (bilirubin limit was 1.5xULN before protocol amendment 1)

Exclusion Criteria

• Participants who had an Eastern Cooperative Oncology Group (ECOG) performance status score ≥3.
• Participants with known leukemic involvement of the central nervous system (CNS).
• Participants who had received treatment with any of the following agents: interferon-alpha within 48 hours, hydroxyurea within 24 hours, homoharringtonine within 14 days, low-dose, moderate dose or high dose cytosine arabinoside within 7, 14 or 28 days respectively, 6-mercaptopurine, vinca alkaloids or steroids within 7 days, anthracyclines, mitoxantrone, etoposide, methotrexate, cyclophosphamide within 21 days, or busulfan within 6 weeks.
• Participants who had undergone hematopoietic stem cell transplantation within six weeks of Day 1, or who had not achieved full hematopoietic recovery following the transplant.
• Participants with grade 3/4 cardiac disease or any serious, concomitant, medical condition.
• Participants with a history of non-compliance to medical regimens or who were considered potentially unreliable.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Dana Faber Cancer Institute

Boston, Massachusetts, United States

New York Presbyterian Hospital

New York, New York, United States

Oregon Health & Sciences University

Portland, Oregon, United States

MD Anderson Cancer Center, University of Texas

Houston, Texas, United States

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

Mannheim, , Germany

Novartis Investigative Site

Monza, , Italy

Novartis Investigative Site

London, , United Kingdom

Countries

United States; France; Germany; Italy; United Kingdom

Other Identifiers

2005-001381-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSTI571A0109E2

Identifier Type: -

Identifier Source: org_study_id