RAD001 in Combination With PKC412 in Patients With Relapsed, Refractory or Poor Prognosis AML or MDS

March 23, 2026 updated by: Richard Stone, MD

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Only one arm on this study.
Drug: RAD001
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.
Other Names:
  • everolimus
Drug: PKC412
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.
Other Names:
  • midostaurin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To determine the toxicities of combination of RAD001 and PKC412.
Time Frame: 2 years
2 years
Observe anti-leukemic effects of this combination including a coda of patients with mutant FLT3 AML.
Time Frame: 2 years
2 years
Measure pharmacokinetics of each agent when administered in combination.
Time Frame: 2 years
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
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Richard Stone, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts General Hospital
Novartis
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Richard Stone, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2009

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2009

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 08-269

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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