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

NCT00819546 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 08-269
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Keywords

AML; MDS

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (4)

• To determine the toxicities of combination of RAD001 and PKC412.

  2 years

• Observe anti-leukemic effects of this combination including a coda of patients with mutant FLT3 AML.

  2 years

• Measure pharmacokinetics of each agent when administered in combination.

  2 years

• Observe the pharmacodynamic effects on the phosphorylation of FLT3 and on activation of relevant signaling pathways and correlate such activation with response.

  2 years

Study Arms (1)

Only one arm on this study.

OTHER

Drug: RAD001; Drug: PKC412

Interventions

RAD001 DRUG

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.

Also known as: everolimus

Only one arm on this study.

PKC412 DRUG

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.

Also known as: midostaurin

Only one arm on this study.

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Richard Stone, MD: lead
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• Brigham and Women's Hospital: collaborator
• Novartis: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Everolimus; midostaurin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Richard Stone, MD

  Dana-Farber Cancer Institute

  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 INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 9, 2009
• Study Start: January 1, 2009
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

US (3)