RAD001 in Patients With Chronic Phase Chronic Myeloid Leukemia w/ Molecular Disease.

NCT01188889 | Withdrawn Phase 1 DMC

• 2 other identifiers: UMCC 2008.093HUM 24993
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

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

  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 (1)

• 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.

Interventions

RAD001 DRUG

Dosing schedule of RAD001 for the Phase I portion: Regimen 1. 5.0 mg q72 hours (400 mg QD); Regimen 2. 5 mg q48 hours (400 mg QD); Regimen 3. 5.0 mg q day (400 mg QD); Regimen 4. 7.5 mg PO q day (400 mg QD.

Imatinib DRUG

Imatinib will be given continuously at a fixed daily dose of 400 mg once daily.

Also known as: Gleevac

Eligibility Criteria

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

You may qualify if:

• Study subjects must be at least age 18 years or older.
• Study subjects must have an Eastern Cooperative Oncology Group performance status 0-2.
• 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.)
• Non-hematologic symptoms related to Imatinib therapy that are ≤ Grade 2 in severity for at least 6 months prior to enrollment.
• Study subjects must meet the following organ function criteria:
• Adequate bone marrow function
• Adequate renal and hepatic function
• International normalized ration \<1.3 (or \<3 on anticoagulants)

You may not qualify if:

• 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.
• Prior external beam radiation therapy to the pelvis.
• Diagnosis of another malignancy, unless disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions: treatment of non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration - with treatment for the condition complete.
• Known chronic condition requiring the treatment with systemic steroids or another immunosuppressive agents.
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Prior seropositive test for the human immunodeficiency virus.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Everolimus; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic 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

• Dale Bixby, M.D., Ph.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 26, 2010
• Study Start: September 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: May 15, 2015

Record last verified: 2015-05

Locations

US (1)