Acute Myeloid LeukemiaPhase 1NCT00819546
RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS
A Phase 1 study testing RAD001 and PKC412 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Richard Stone, MD at 3 sites in United States.
Trial summary
The purpose of this research study is to determine the safety of the combination of RAD001 and PKC412 as a cancer treatment, and to establish the highest dose of RAD001 that can be given in conjunction with PKC412. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- RAD001 and PKC412
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2009to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Cytopathologically or histopathologically confirmed diagnosis of AML, MDS (RAEB-1, -2) or CMML, who are either relapsed or refractory to standard therapy, or are considered inappropriate candidates for standard therapy.
- Inappropriateness for standard therapy requires a) MDS patients: not be a candidate for immediate allogeneic stem cell transplantation, not have a -5q-cytogenetic abnormality (unless previously received lenalidomide), and not be an appropriate candidate for a DNA hypomethylating agent b) AML patients must be 60 years of age or greater and have one of more of the following documented poor risk factors: ECOG Performance Status = 2, 70 years of age or older, unfavorable cytogenetics.
- Life expectancy of at least 12 weeks
- Not likely to require cytoreductive therapy within one month (other than hydroxyurea)
- ECOG Performance Status of 2 or less
- Serum transaminase activity (AST/SGOT \& ALT/SGPT) < 2.5 x ULN
Show all 9Show fewer
- Serum total bilirubin < 1.5 x ULN ( with the exception of individuals with Gilbert's disease)
- INR < 1.3 (or < 3 on anticoagulants)
- Fasting serum cholesterol 300mg/dl or 7.75 mmol/L or less AND fasting triglycerides 2.5 ULN or less
Who cannot join
- Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously
- Female patients who are pregnant or breast feeding or adults of child bearing not employing double barrier contraception
- Concurrent severe and/or uncontrolled medical or psychiatric condition which may interfere with the completion of the study
- Impairment of gastrointestinal function or GI disease that may significantly alter absorption of PKC412 or RAD001
- Uncontrolled active infection
- Any pulmonary infiltrate on teh baseline chest x-ray known to be new in the previous 4 weeks
Show all 17Show fewer
- Patients with a Grade 2 or higher hypercholesterolemia or hypertriglyceridemia despite lipid-lowering therapy
- Patients with history of another malignancy within the past 5 years, with the exception of adequately treated basal or squamous cell skin carcinoma or cervical carcinoma in situ
- History of non-compliance to medical regimens and patients who are unwilling or unable to comply with this protocol
- Prior treatment with any investigational drug within preceding 4 weeks
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
- Any severe or uncontrolled medical conditions or other conditions that could affect their participation
- Known history of HIV seropositivity
- Known hypersensitivity to RAD001 or other rapamycins or to its excipients
- Known hypersensitivity to PKC412 or to its excipients
- Diagnosis of acute promyelocytic leukemia
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Phase I Trial of Escalating Dose of RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS
The purpose of this research study is to determine the safety of the combination of RAD001 and PKC412 as a cancer treatment, and to establish the highest dose of RAD001 that can be given in conjunction with PKC412. These drugs have been used in other research trials for individuals with solid and hematology malignancies. Past research on PKC412 shows that it blocks the abnormal functioning of an enzyme called FLT3. FLT3 is found in your cells in either a normal (wild type) or genetically changed form and plays a role in the survival and growth of AML cells. RAD001 is an inhibitor of a central growth pathway that involves the protein MTOR. The MTOR pathway is overactive in cancer cells, causing the cells to grow abnormally. By inhibiting the abnormal growth activity of the MTOR pathway, RAD001 slows down and possibly stops the growth of cancer cells.
Read the detailed description
- This is a dose-escalation study in which 3 participants will be given a particular starting dose of RAD001 on a certain schedule. If the dose and schedule are well tolerated, then the next 3 participants enrolled will be assigned a new dosing schedule and/or a higher dose of RAD001. This will continue until a maximum tolerated dose (MTD) is reached for RAD001.
- Each cycle of treatment consists of 28 days on an outpatient basis. Participants will receive RAD001 as the assigned schedule and dosage on day 1 and on days 8 through 28 for the first cycle. For all subsequent cycles RAD001 will be taken once daily. Additionally, all participants will take PKC412 twice a day on days 2 through 28 for the first cycle. For all subsequent cycles PKC412 will be taken twice daily.
- During the course of the trial the following evaluations and procedures will be completed at various times: review of medical history; review of concomitant medications; physical exam; performance status; vital signs; EKG; chest x-ray; blood tests and bone marrow aspirate/biopsy.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Being tested
- RAD001, PKC412
- Keywords
- AML, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called everolimus
Participants will receive RAD001 on day 1 at the dose specified then again on days 8-28 for the first cycle. For all subsequent cycles RAD001 will be taken once daily.
PKC412Drug
Also called midostaurin
50mg orally twice a day on days 2-28 for the first cycle. For all subsequent cycles 50mg of PKC412 will be taken orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Only one arm on this study. | Other | Not described Receives: Drug: RAD001; Drug: PKC412 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify the maximum tolerated dose of RAD001 that can be given in combination with twice daily PKC412 in patients who are non-chemotherapy candidates with AML or MDS.
Measured: 2 years
Secondary outcomes (4)
To determine the toxicities of combination of RAD001 and PKC412.
Measured: 2 years
Observe anti-leukemic effects of this combination including a coda of patients with mutant FLT3 AML.
Measured: 2 years
Measure pharmacokinetics of each agent when administered in combination.
Measured: 2 years
Observe the pharmacodynamic effects on the phosphorylation of FLT3 and on activation of relevant signaling pathways and correlate such activation with response.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Richard Stone, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Novartis
- Responsible party
- Sponsor-investigator, Richard Stone, MD, Dana-Farber Cancer Institute
- Investigators
- Richard Stone, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00819546
- Sponsor's protocol ID
- 08-269
- Status last verified
- Mar 2026
- First submitted
- 8 Jan 2009
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Escalating Dose of RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS
- ClinicalTrials.gov ID
- NCT00819546
- Acronym / sponsor ID
- 08-269
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Keywords
- AML, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Richard Stone, MDUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Novartis
- Study start
- Jan 2009
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 9 Jan 2009 (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.
The purpose of this research study is to determine the safety of the combination of RAD001 and PKC412 as a cancer treatment, and to establish the highest dose of RAD001 that can be given in conjunction with PKC412. These drugs have been used in other research trials for individuals with solid and hematology malignancies. Past research on PKC412 shows that it blocks the abnormal functioning of an enzyme called FLT3. FLT3 is found in your cells in either a normal (wild type) or genetically changed form and plays a role in the survival and growth of AML cells. RAD001 is an inhibitor of a central growth pathway that involves the protein MTOR. The MTOR pathway is overactive in cancer cells, causing the cells to grow abnormally. By inhibiting the abnormal growth activity of the MTOR pathway, RAD001 slows down and possibly stops the growth of cancer cells.
Detailed description
- This is a dose-escalation study in which 3 participants will be given a particular starting dose of RAD001 on a certain schedule. If the dose and schedule are well tolerated, then the next 3 participants enrolled will be assigned a new dosing schedule and/or a higher dose of RAD001. This will continue until a maximum tolerated dose (MTD) is reached for RAD001.
- Each cycle of treatment consists of 28 days on an outpatient basis. Participants will receive RAD001 as the assigned schedule and dosage on day 1 and on days 8 through 28 for the first cycle. For all subsequent cycles RAD001 will be taken once daily. Additionally, all participants will take PKC412 twice a day on days 2 through 28 for the first cycle. For all subsequent cycles PKC412 will be taken twice daily.
- During the course of the trial the following evaluations and procedures will be completed at various times: review of medical history; review of concomitant medications; physical exam; performance status; vital signs; EKG; chest x-ray; blood tests and bone marrow aspirate/biopsy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Only one arm on this study. | Other | Drug: RAD001, Drug: PKC412 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cytopathologically or histopathologically confirmed diagnosis of AML, MDS (RAEB-1, -2) or CMML, who are either relapsed or refractory to standard therapy, or are considered inappropriate candidates for standard therapy.
- Inappropriateness for standard therapy requires a) MDS patients: not be a candidate for immediate allogeneic stem cell transplantation, not have a -5q-cytogenetic abnormality (unless previously received lenalidomide), and not be an appropriate candidate for a DNA hypomethylating agent b) AML patients must be 60 years of age or greater and have one of more of the following documented poor risk factors: ECOG Performance Status = 2, 70 years of age or older, unfavorable cytogenetics.
- Life expectancy of at least 12 weeks
- Not likely to require cytoreductive therapy within one month (other than hydroxyurea)
- ECOG Performance Status of 2 or less
Key exclusion criteria (17 listed)
- Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously
- Female patients who are pregnant or breast feeding or adults of child bearing not employing double barrier contraception
- Concurrent severe and/or uncontrolled medical or psychiatric condition which may interfere with the completion of the study
- Impairment of gastrointestinal function or GI disease that may significantly alter absorption of PKC412 or RAD001
- Uncontrolled active infection
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 |
|---|---|---|
| RAD001Also: everolimusParticipants will receive RAD001 on day 1 at the dose specified then again on days 8-28 for the first cycle. For all subsequent cycles RAD001 will be taken once daily. | Drug | Only one arm on this study. |
| PKC412Also: midostaurin50mg orally twice a day on days 2-28 for the first cycle. For all subsequent cycles 50mg of PKC412 will be taken orally twice daily. | Drug | Only one arm on this study. |
Primary outcome
To identify the maximum tolerated dose of RAD001 that can be given in combination with twice daily PKC412 in patients who are non-chemotherapy candidates with AML or MDS.
Time frame: 2 years
4 secondary outcomes
To determine the toxicities of combination of RAD001 and PKC412.
Time frame: 2 years
Observe anti-leukemic effects of this combination including a coda of patients with mutant FLT3 AML.
Time frame: 2 years
Measure pharmacokinetics of each agent when administered in combination.
Time frame: 2 years
Observe the pharmacodynamic effects on the phosphorylation of FLT3 and on activation of relevant signaling pathways and correlate such activation with response.
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2026.
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Richard Stone, MD principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RAD001 and PKC412 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Richard Stone, MD at 3 sites 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 9 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
To identify the maximum tolerated dose of RAD001 that can be given in combination with twice daily PKC412 in patients who are non-chemotherapy candidates with AML or MDS. (time frame: 2 years). 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 25 Mar 2026.