Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia - Full Text View

Sponsors and Collaborators:	Oregon Health and Science University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00015847

Purpose

RATIONALE: Imatinib mesylate and interferon alfa may interfere with the growth of the cancer cells. Combining imatinib mesylate with interferon alfa may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with interferon alfa in treating patients who have chronic myelogenous leukemia.

Condition	Intervention	Phase
Leukemia	Biological: recombinant interferon alfa Drug: imatinib mesylate	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Interferon alfa-2a Imatinib Imatinib mesylate Interferon alfa-n1 Interferons

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-Alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Treatment-related toxicity (i.e., grade 3 or 4 nonhematologic toxicity) as measured by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
Complete and major cytogenetic response at 6 and 12 months (Phase II) [ Designated as safety issue: No ]
Minor cytogenetic response at 6 and 12 months (Phase II) [ Designated as safety issue: No ]
Complete hematologic response at 6 and 12 months (Phase II) [ Designated as safety issue: No ]
Molecular response in patients with complete cytogenetic response at 6 and 12 months (Phase II) [ Designated as safety issue: No ]

Study Start Date:

April 2001

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of interferon alfa administered with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)
Determine the safety and tolerability of this regimen in this patient population.
Determine the complete, major, and minor cytogenetic response rates and complete hematologic response rate in patients after 6 and 12 months of treatment with this regimen.
Determine the molecular response (reverse transcriptase-polymerase chain reaction for bcr-abl) rate in patients who have a complete cytogenetic response after 6 and 12 months of treatment with this regimen.
Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Phase I (closed to accrual as of 7/9/03): Patients receive oral imatinib mesylate once daily beginning on day 1 and interferon alfa (IFN-A) subcutaneously once daily or 3 times weekly beginning on day 14. Courses repeat every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of 1 year of therapy, patients may receive additional therapy, provided that the patient is benefiting from imatinib mesylate. IFN-A is discontinued in patients who achieve a molecular remission that is confirmed on 2 successive bone marrow samples. Imatinib mesylate is discontinued in patients who achieve and maintain a molecular remission for 2 years.

Sequential dose escalation of IFN-A is followed by sequential dose escalation of imatinib mesylate. Cohorts of 3-6 patients receive escalating doses of IFN-A and then imatinib mesylate until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for the phase I portion of this study. (Phase I closed to accrual as of 7/9/03.) A total of 40 patients will be accrued for the phase II portion of the study within 3-4 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Cytogenetically confirmed chronic myelogenous leukemia (CML)
- Less than 15% blasts in peripheral blood or bone marrow
- Less than 30% blasts and promyelocytes in peripheral blood or bone marrow
- Less than 20% basophils in blood or bone marrow
- Platelet count at least 100,000/mm^3
No leukemia beyond bone marrow, blood, liver, or spleen
No chloroma
Phase I (closed to accrual as of 7/9/03):
- Philadelphia (Ph) chromosome-positive CML in chronic phase
Phase II:
- Newly diagnosed Ph chromosome-positive CML in chronic phase
- Initial diagnosis within 6 months of study
- No prior therapy for CML except hydroxyurea and/or anagrelide hydrochloride
Phase I (closed to accrual as of 7/9/03) and II:
- No identified sibling donors where allogeneic stem cell transplantation is elected as first-line therapy

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST or ALT no greater than 2 times ULN

Renal:

Creatinine no greater than 1.5 times ULN

Cardiovascular:

No New York Heart Association class III or IV heart disease

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use 2 methods of effective barrier contraception during and for at least 3 months after study participation
No other serious uncontrolled medical condition
No autoimmune disease
No prior noncompliance to medical regimens or potential unreliability
No prior grade 3 or greater non-hematologic toxicity due to prior interferon (phase I [closed to accrual as of 7/9/03])

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No prior bone marrow or peripheral blood stem cell transplantation
At least 2 weeks since prior interferon alfa (phase I [closed to accrual as of 7/9/03])

Chemotherapy:

See Disease Characteristics
At least 6 weeks since prior busulfan (phase I [closed to accrual as of 7/9/03] )
At least 2 weeks since prior cytarabine (phase I [closed to accrual as of 7/9/03])
No concurrent chemotherapy
Concurrent hydroxyurea allowed during the first 3 months of study

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

At least 4 weeks since prior investigational agents other than imatinib mesylate (phase I [closed to accrual as of 7/9/03])
No concurrent grapefruit juice
Concurrent anagrelide hydrochloride allowed during the first 3 months of study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00015847

Locations

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239

Sponsors and Collaborators

Oregon Health and Science University

National Cancer Institute (NCI)

Investigators

Study Chair:

Brian J. Druker, MD

Oregon Health and Science University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000068443, OHSU-6263, NCI-2794
Study First Received:	May 6, 2001
Last Updated:	April 4, 2009
ClinicalTrials.gov Identifier:	NCT00015847 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Study placed in the following topic categories:

Philadelphia Chromosome
Interferon-alpha
Interferon Type I, Recombinant
Immunologic Factors
Hematologic Diseases
Interferons
Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Protein Kinase Inhibitors

Angiogenesis Inhibitors
Antiviral Agents
Imatinib
Leukemia
Signs and Symptoms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia
Bone Marrow Diseases
Interferon Alfa-2a

Additional relevant MeSH terms:

Anti-Infective Agents
Interferon Type I, Recombinant
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Leukemia
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Interferon-alpha
Neoplasms by Histologic Type
Hematologic Diseases

Growth Substances
Interferons
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Imatinib
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon Alfa-2a
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 06, 2009