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

Novartis

Status and phase: Completed; Phase 2

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

Treatments: Drug: STI571 400 mg; Drug: STI571 600 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00171249

CSTI571A0109E2

2005-001381-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 293 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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293 participants in 7 patient groups

Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 400 mg

Lymphoid Blast Crisis 400 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 400 mg

Acute Lymphoblastic Leukemia 400 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 400 mg

Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 600 mg

Lymphoid Blast Crisis 600 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 600 mg

Acute Lymphoblastic Leukemia 600 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 600 mg

Acute Myeloid/Myelogenous Leukemia 600 mg

Experimental group

Description:

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.

Treatment:

Drug: STI571 600 mg