Everolimus and Imatinib Mesylate in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia Who Are Not in Complete Cytogenetic Remission After Previous Imatinib Mesylate

NCT00093639 | Completed Phase 1

• 4 other identifiers: NOVARTIS-CRAD001C2207RPCI-PH-24204CDR0000389252NCI-2010-00894
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as everolimus, work in different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Combining everolimus with imatinib mesylate may be effective in killing cancer cells that have become resistant to imatinib mesylate. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with imatinib mesylate and to see how well they work in treating patients with chronic phase chronic myelogenous leukemia who are not in complete cytogenetic remission after previous imatinib mesylate.

Conditions

Leukemia

Keywords

chronic phase chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive

Outcome Measures

Primary Outcomes (1)

• Tolerability and biological activity of everolimus and imatinib mesylate every 6 months after completion of study treatment

Secondary Outcomes (6)

• Cytogenetic improvements at 3 and 6 months and then every 6 months after completion of study treatment

• Changes in the amounts of the Bcr-Abl transcripts as measured by quantitative real time reverse transcriptase PCR (QT-PCR) every 6 months after completion of study treatment

• mTOR pathway activity at baseline and during treatment measured by molecular pathological examination of blood and bone marrow cells every 6 months after completion of study treatment

• Disease-related mutations and gene expression changes in blood, bone marrow cells, and in plasma every 6 months after completion of study treatment

• Effects of genetic variation in drug metabolism genes, leukemia genes, and drug target genes on patient response measured every 6 months after completion of study treatment

Interventions

everolimus DRUG

imatinib mesylate DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed chronic myelogenous leukemia (CML) * In chronic phase * Philadelphia chromosome (Ph)-positive * No accelerated or blastic phase * Accelerated phase CML is defined as ≥ 15% but \< 30% blasts in peripheral blood or bone marrow OR ≥ 30% blasts and promyelocytes in peripheral blood or bone marrow provided that \< 30% blasts were present OR ≥ 20% peripheral basophils OR platelet count \< 100,000/mm\^3, unrelated to therapy * No less than 20 metaphases in the bone marrow sample * No evidence of complete cytogenetic response to imatinib mesylate (complete cytogenetic response defined as 0% Ph-positive cells in bone marrow) * Receiving continuous imatinib mesylate therapy for ≥ the past 9 months * Dosage ≥ 600 mg/day for ≥ the past 3 months * Stable dose of 600 mg/day for ≥ the past 4 weeks * Achieved and maintained hematological response to imatinib mesylate as defined by all of the following: * WBC \< 20,000/mm\^3 * Basophils \< 20% * Less than 5% myelocytes and metamyelocytes in peripheral blood * No blasts or promyelocytes in peripheral blood * No evidence of disease-related symptoms or extramedullary disease, including enlarged spleen or liver PATIENT CHARACTERISTICS: Age * 18 and over Performance status * WHO 0-2 Life expectancy * Not specified Hematopoietic * See Disease Characteristics * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL Hepatic * AST and ALT \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN (except for patients with Gilbert's disease) * PTT \< 1.5 times ULN (except for patients on oral anticoagulation therapy) * INR \< 1.5 times ULN (except for patients on oral anticoagulation therapy) Renal * Creatinine \< 1.5 times ULN Cardiovascular * No angina * No New York Heart Association class III or IV cardiac disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 3 months after study participation * HIV negative * No history of non-compliance with medical regimens * No hypercholesterolemia or hypertriglyceridemia (fasting state) ≥ grade 2 (despite lipid-lowering therapy) * No diabetes mellitus * No thyroid dysfunction * No neuropsychiatric disorders * No infection * No other severe and/or uncontrolled medical condition that would preclude study participation * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * No prior allogeneic, syngeneic, or autologous bone marrow transplantation or stem cell transplantation for CML * No concurrent prophylactic hematopoietic growth factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or epoetin alfa) Chemotherapy * No prior chemotherapy regimens used in transplantation Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Recovered from prior major surgery Other * No prior sirolimus in combination with imatinib mesylate * At least 4 weeks since prior investigational agents used in combination with imatinib mesylate and recovered * No other concurrent investigational therapies * No other concurrent anticancer agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Everolimus; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Meir Wetzler, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2004
• First Posted: October 8, 2004
• Study Start: August 1, 2004
• Primary Completion: August 1, 2006
• Study Completion: August 1, 2006
• Last Updated: May 1, 2013

Record last verified: 2013-04

Locations

US (1)