RAD001 + PKC412 for Acute Myeloid Leukemia
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to test the safety of using two drugs, RAD001 (an mTOR inhibitor) and PKC412 (a kinase inhibitor), together to treat certain blood cancers, such as acute myeloid leukemia (AML). The trial examines how effectively these drugs work together to block growth signals in cancer cells, slowing or stopping their spread. Individuals with AML or similar blood disorders who have not responded to standard treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on chronic treatment with systemic steroids or another immunosuppressive agent.
Is there any evidence suggesting that the combination of RAD001 and PKC412 is likely to be safe for humans?
Research has shown that using RAD001 and PKC412 together to treat acute myeloid leukemia (AML) raises some safety concerns. In earlier studies, PKC412, also known as midostaurin, caused side effects, with about 65% of patients experiencing mild to moderate stomach problems. A few cases of serious lung issues were fatal.
RAD001, also called everolimus, helps slow the growth of cancer cells. While specific safety information on using RAD001 and PKC412 together is limited, both drugs have been studied in other cancer treatments, providing some understanding of their safety. As this is a Phase 1 trial, the main goal is to determine the safest dose, so current safety information might be limited. This trial aims to assess how well patients tolerate these drugs when used together.12345Why do researchers think this study treatment might be promising?
Researchers are excited about the combination of RAD001 and PKC412 for Acute Myeloid Leukemia (AML) because it targets the disease in a unique way. Unlike traditional chemotherapy, which attacks rapidly dividing cells, PKC412 specifically inhibits a protein called FLT3 that is often mutated in AML, potentially leading to more targeted treatment with fewer side effects. Meanwhile, RAD001 works by inhibiting mTOR, a pathway that cancer cells use to grow and survive. By combining these two drugs, the treatment aims to attack the cancer from multiple angles, potentially improving outcomes for patients with AML who have limited options with standard therapies.
What evidence suggests that the combination of RAD001 and PKC412 might be an effective treatment for Acute Myeloid Leukemia?
Research has shown that a drug called PKC412, or midostaurin, helps patients with acute myeloid leukemia (AML) live longer. In one study, patients taking midostaurin had better survival rates than those who did not. Another drug, RAD001, targets a protein called MTOR, which is often overactive in cancer cells, helping to slow or stop their growth. This trial tests the combination of RAD001 and PKC412, as it might block cancer growth in two different ways. Early results suggest that these drugs may work well together to treat AML more effectively.13678
Who Is on the Research Team?
Richard Stone, MD
Principal Investigator
Dana-Farber Cancer Institute
Are You a Good Fit for This Trial?
This trial is for adults with relapsed or refractory AML, MDS, or CMML who can't have standard therapy. They should be in relatively stable health (ECOG ≤2), not pregnant, using double barrier contraception if of childbearing potential, and without recent transplants or other cancers within 5 years.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive RAD001 and PKC412 in a dose-escalation study to determine the maximum tolerated dose
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- PKC412
- RAD001
Find a Clinic Near You
Who Is Running the Clinical Trial?
Richard Stone, MD
Lead Sponsor
Novartis
Industry Sponsor
Vasant Narasimhan
Novartis
Chief Executive Officer since 2018
MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government
Shreeram Aradhye
Novartis
Chief Medical Officer since 2022
MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania
Beth Israel Deaconess Medical Center
Collaborator
Massachusetts General Hospital
Collaborator
Brigham and Women's Hospital
Collaborator