Clinical trial NCT00171249: An Extension Study to Determine the Safety and Anti-Leukemic Effects of Imatinib Mesylate in Adult Participants With Ph+ Leukemia
Official title: An Extension to a Phase II Study to Determine the Safety and Anti-Leukemic Effects of STI571 in Adult Patients With Philadelphia Chromosome Positive Leukemia Including Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Accelerated Phase Chronic Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Philadelphia Positive Chronic Myeloid Leukemia
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Keywords: Chronic Myelogenous Leukemia
CML
Philadelphia Chromosome
Accelerated phase
Acute Myelogenous Leukemia
AML
Acute Lymphoblastic Leukemia
ALL
Imatinib mesylate
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 293
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: Up to 3 years after start of treatment
Secondary outcomes:
measure: Percentage of Participants With Cytogenetic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: Up to 3 years after start of treatment
measure: Time to Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: Up to 3 years after start of treatment
measure: Duration of Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: Up to 3 years after start of treatment
measure: Time to Progression to Blast Crisis in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: Up to 3 years after start of treatment
measure: Overall Survival by Disease
timeFrame: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 months after start of treatment
measure: Overall Survival by Dose in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia
timeFrame: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 months after start of treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center, University of Texas
state: Texas
city: Pessac
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: