Chronic Myeloid LeukemiaPhase 1/2NCT01188889
RAD001 in Patients With Chronic Phase Chronic Myeloid Leukemia w/ Molecular Disease.
A Phase 1/2 study testing RAD001 and Imatinib in people with Chronic Myeloid Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- RAD001 and Imatinib
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Dec 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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)
- Study subjects must meet the following cardiac function criteria:
- No history of uncontrolled angina, congestive heart failure or myocardial infarction within 6 months of study entry. If there is a suspected clinical history of coronary artery disease, then the patient must document one of the following within 1 year of study participation:Left ventricular ejection fraction greater than 40% on multigated acquisition scan or similar radionuclide angiographic scan; or Left ventricular fractional shortening greater than 22% on echocardiography exam; or LVEF greater than 40% on echocardiography exam.
- No history of a diagnosis or suspected congenital QRS complex to the end of the T wave on an electrocardiogram syndrome.
- No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
- No history of uncontrolled hypertension.
Who cannot join
- 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.
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- 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.
- Uncontrolled diabetes mellitus
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo therapy with RAD001 including:severely impaired lung function; liver disease such as cirrhosis, chronic active hepatitis or chronic; persistent hepatitis;other nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy.
- History of significant bleeding disorder unrelated to cancer, including:Congenital bleeding disorders (e.g., von Willebrand's disease); Acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Health System
Ann Arbor, Michigan, 48109
About this study
Official title: 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.
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
- Being tested
- RAD001, Imatinib
- Keywords
- Chronic Myeloid Leukemia
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
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.
ImatinibDrug
Also called Gleevac
Imatinib will be given continuously at a fixed daily dose of 400 mg once daily.
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective will assess for the maximum tolerated dose of RAD001 when combined with a fixed dose of Imatinib.
Measured: 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.
Measured: This objective will be assessed by RT-PCR for the Bcr-Abl gene product as demonstrated by the degree of complete molecular responses.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2010 (estimated)
- Study startSep 2013
- Primary completionDec 2016 (estimated)
- Study completionDec 2017 (estimated)
Why it stopped: Unable to obtain sufficient funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Dale Bixby, M.D., Ph.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01188889
- Sponsor's protocol ID
- UMCC 2008.093
- Other IDs
- HUM 24993
- Status last verified
- May 2015
- First submitted
- 25 Aug 2010
- Last updated
- 15 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT01188889
- Acronym / sponsor ID
- UMCC 2008.093
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Chronic Myeloid Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to obtain sufficient funding.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Sep 2013
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 26 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Dosing 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. | Drug | – |
| ImatinibAlso: GleevacImatinib will be given continuously at a fixed daily dose of 400 mg once daily. | Drug | – |
Primary outcome
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.
1 secondary outcome
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.
Time frame: This objective will be assessed by RT-PCR for the Bcr-Abl gene product as demonstrated by the degree of complete molecular responses.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dale Bixby, M.D., Ph.D. principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RAD001 and Imatinib in people with Chronic Myeloid Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2015.