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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00171249
• Other study ID #: CSTI571A0109E2
• Secondary ID: 2005-001381-14
• Status: Completed
• Phase: Phase 2
• Start date: August 9, 1999
• Est. completion date: September 23, 2013

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 293
• Est. completion date: September 23, 2013
• Est. primary completion date: September 23, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• STI571 400 mg
STI571 capsules and tablets
• STI571 600 mg
STI571 capsules and tablets

Locations

Country	Name	City	State
France	Novartis Investigative Site	Pessac
France	Novartis Investigative Site	Poitiers
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Italy	Novartis Investigative Site	Monza
United Kingdom	Novartis Investigative Site	London
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center, University of Texas	Houston	Texas
United States	New York Presbyterian Hospital	New York	New York
United States	Oregon Health & Sciences University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	Hematologic response was evaluated from hematology measurements in the peripheral blood (PB) and bone marrow (BM) and assessments of extramedullary leukemic involvement (EMD) at physical examination. Response was defined as complete hematologic remission (CHR), no evidence of leukemia (NEL), or return to chronic phase (RTC).	Up to 3 years after start of treatment
Secondary	Percentage of Participants With Cytogenetic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	Bone marrow (BM) cytogenetic analysis was required at baseline, after 12 weeks (visit 22) and after 24 weeks (visit 28) to evaluate Ph chromosome positivity. In several participants, this was also done after 4 and 8 weeks. Based on the percentage of Philadelphia chromosome positive (Ph+) cells = (positive cells/examined cells)x100, at each BM assessment the cytogenetic response was classified as: Complete, 0% Ph+ cells; Partial, >0 - 35% Ph+ cells; Minor, >35 - 65% Ph+ cells; Minimal, >65 - 95% Ph+ cells; None, >95% Ph+ cells; Not done: <20 metaphases were examined and/or response could not be assigned. Cytogenetic response was defined as confirmed complete or partial response. A BM sample was considered as assessable for cytogenetic response only if it contained =20 metaphases. However, an assessment of partial response was retained in a sample with <20 metaphases when it was immediately preceded or followed by a complete or partial response in another sample with =20 metaphases.	Up to 3 years after start of treatment
Secondary	Time to Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	Time to response was defined for all participants as the time until first documented response (which was confirmed =4 weeks later).	Up to 3 years after start of treatment
Secondary	Duration of Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	Duration of response was defined as the time between first documented response (which was confirmed =4 weeks later) and the earliest date of the following: loss of response (when any of the criteria for response were no longer fulfilled); progression to blast crisis (=30% blasts in peripheral blood or bone marrow, extramedullary involvement other than liver/spleen enlargement); discontinuation due to adverse event, laboratory abnormality, unsatisfactory therapeutic effect or death.	Up to 3 years after start of treatment
Secondary	Time to Progression to Blast Crisis in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	Progression to blast crisis was defined as =30% blasts in peripheral blood or bone marrow or as extramedullary involvement other than liver or spleen enlargement.	Up to 3 years after start of treatment
Secondary	Overall Survival by Disease	To evaluate overall survival, all participants were followed after the last dose of study drug every month for the first three months and thereafter every three months until death. Overall survival was calculated for all participants as the time between start of treatment and death due to any reason. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up. For participants without survival follow-up information, the time was censored at last available visit/treatment date.	12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 months after start of treatment
Secondary	Overall Survival by Dose in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia	To evaluate overall survival, all participants were followed after the last dose of study drug every month for the first three months and thereafter every three months until death. Overall survival was calculated for all participants as the time between start of treatment and death due to any reason. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up. For participants without survival follow-up information, the time was censored at last available visit/treatment date.	12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 months after start of treatment