An Open Label, Time-To-Event Continuous Reassessment Method, Phase I/II Study of the Mammalian Target of Rapamycin (mTOR) Inhibitor RAD001 in Combination With Imatinib (Gleevec) in Patients With Chronic Phase Chronic Myeloid Leukemia (CML) With Persistent Molecular Disease.

University of Michigan Rogel Cancer Center1 site in 1 countrySeptember 2013

ConditionsChronic Myeloid Leukemia

DrugsRAD001 Imatinib

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Chronic Myeloid Leukemia
Sponsor: University of Michigan Rogel Cancer Center
Locations: 1
Primary Endpoint: The primary objective will assess for the maximum tolerated dose of RAD001 when combined with a fixed dose of Imatinib.
Status: Withdrawn
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Patients participating in this study will have a diagnosis of Chronic Myeloid Leukemia. This study will evaluate whether the addition of an investigational drug called RAD001 given together with Imatinib will better target leukemia stem cells, causing them to die. Stem cells are a small population of cells, existing primarily within the bone marrow, and are believed to be responsible for the ongoing risk of disease relapse.

Registry

clinicaltrials.gov

Start Date

September 2013

End Date

December 2017

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Study subjects must be at least age 18 years or older.
•Study subjects must have an Eastern Cooperative Oncology Group performance status 0-
•Study subjects must provide a signed written informed consent.
•Study subjects must be able to comply with study procedures and follow-up examinations.
•Female study subjects: non-fertile (status post hysterectomy (removal of the uterus) or menopausal (no menstrual period) for 24 consecutive months or agree to use birth control during the study through the end of last treatment visit. Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to administration of RAD001). Use of a single agent for prevention of pregnancy (oral, implantable, or injectable contraceptives) may be affected by medications that alter the activity of the cytochrome P450 enzyme, and are therefore, not considered effective during participation in this clinical trial.If there is ANY chance that pregnant can occur, there must be a commitment to continue abstinence from heterosexual intercourse or begin TWO methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME.
•There must be at least two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
•Study subjects must meet the following disease criteria:
•Diagnosis of Chronic Myelogenous Leukemia according to the World Health Organization.
•Persistent molecular disease as defined by the persistent identification of the Bcr-Abl transcript using quantitative RT-PCR on at least 2 occasions at least 3 months apart and having completed a minimum of 18 months of treatment with Imatinib at 400 mg once daily.
•Achieved a complete cytogenetic response. (This shall be measured at least one time prior to consent to participation in the clinical trial, and shall be reassessed at the initiation of the clinical trial.)

Exclusion Criteria

•Study subjects may not have had prior treatment with RAD001, sirolimus, temsirolimus, or rapamycin.
•Study subjects may not have a known hypersensitivity to RAD001 or other rapamycin, sirolimus, temsirolimus or to its excipients.
•Study subjects may not have received an investigational agent received within 28 days prior to the first dose of study drug.
•Study subjects may not have psychiatric disorders that would interfere with consent, study participation, or follow-up.
•Study subjects may not have a history of noncompliance to medical regimens.
•Study subjects unwilling to or unable to comply with the protocol are not eligible to participate in this clinical research trial.
•Study subjects that meet any of the following criteria are not eligible to participate in the clinical research study:
•Diagnosis of an accelerated phase or a blast phase of chronic myeloid leukemia according to the World Health Organization criteria.
•Clinical evidence suggestive of central nervous system involvement with leukemia unless a lumbar puncture confirms the absence of leukemia in the cerebrospinal fluid.
•Prior hematopoietic stem cell transplant.

Outcomes

Primary Outcomes

The primary objective will assess for the maximum tolerated dose of RAD001 when combined with a fixed dose of Imatinib.

Time Frame: This objective will assessed by a time-to-event, continuous reassessment method to establish the maximun tolerated dose of the combination of a fixed dose of Imatinib together with RAD001.

Secondary Outcomes

The objective will assess the degree to which a fixed dose of Imatinib combined with RAD001 given at the maximum tolerated dose is able to deplete the pool of minimal residual disease in patients.(This objective will be assessed by RT-PCR for the Bcr-Abl gene product as demonstrated by the degree of complete molecular responses.)