PANAML: Panobinostat, Fludarabine and Cytarabine in Patients with AML or MDS

A Phase I and Dose Expansion Cohort Study of Panobinostat in Combination with Fludarabine and Cytarabine in Pediatric Patients with Refractory or Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome

Categories:

Leukemia / Lymphoma

Phase I/II

Diseases Treated:

Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)

Eligibility Overview:

  • Diagnosis of AML or MDS that has come back or did not respond to chemotherapy
  • 21 years of age or younger at time of enrollment
  • Able to swallow capsules
  • Recovered from side effects of previous cancer therapy
  1. Brief Summary

    This clinical trial will evaluate a new therapy for relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in children, adolescents and young adults up to 21 years old. Current treatment for these diseases often relies on a combination of the chemotherapy drugs, fludarabine and cytarabine. This study will add a third drug, panobinostat, to this regimen. Panobinostat is a histone deacetylase (HDAC) inhibitor that has been approved for the treatment of adults with multiple myeloma. It has not been approved to treat leukemia or MDS and has not been approved for pediatric use. It has never been tested in combination with fludarabine and cytarabine.

    The study will test the safety and effectiveness of panobinostat when combined with a chemotherapy regimen using fludarabine and cytarabine.

    Primary Objective

    • To determine the maximum tolerated dose of panobinostat when given in combination with fludarabine and cytarabine in pediatric patients with relapsed or refractory AML or MDS.

    Secondary Objectives

    • To find out if the combination therapy is safe and effective in pediatric patients.
    • To document side effects of the therapy.
    • To learn more about the way panobinostat is absorbed and distributed in the body.

    Eligibility

    Inclusion criteria (among others)

    • Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has relapsed or is refractory to chemotherapy or that has relapsed after hematopoietic stem cell transplantation (HSCT)
    • Adequate organ function
    • ≤21 years old
    • Able to swallow capsules
    • Recovered from acute effects of prior cancer therapy

    Exclusion Criteria (among others)

    • Pregnant or lactating
    • Diagnosed with one of the following:
      • Down syndrome
      • Acute promyelocytic leukemia
      • Juvenile myelomonocytic leukemia
      • Fanconi anemia
      • Kostmann syndrome, Shwachmann syndrome or other bone marrow failure syndrome
    • Has taken another investigational drug within the previous 30 days.
    • Known HIV infection 
    • Experiencing significant diarrhea
    • Known impaired cardiac function/disease or impaired GI function/disease

    View the full study protocol at clinicaltrials.gov

  2. About this clinical trial

    This study is for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has not improved with chemotherapy or has come back after chemotherapy. AML is a cancer of the white blood cells. MDS is a bone marrow cancer that reduces the body’s production of normal blood cells.

    Doctors have used chemotherapy drugs to treat childhood leukemia in many children successfully. However, some of these children eventually relapse and the cancer comes back. In some cases, the chemotherapy may not work at all. In this study, St. Jude researchers will add a new drug called panobinostat to standard chemotherapy.

    Purpose of this clinical trial

    The main goal of this study is to find the strongest but safest dose of the drug panobinostat when it is combined with fludarabine and cytarabine. They also want to see how well this combination treats AML and MDS. . Fludarabine and cytarabine are two common chemotherapy drugs often used to treat childhood leukemia. Panobinostat is approved to treat adults with another type of cancer, but it has not been approved to treat leukemia or MDS. It has also not been approved as a treatment for children.

    Doctors will try to find the highest dose of panobinostat that can be given safely to children. They will also look for any side effects and take blood samples to see how well the body absorbs the drug and how long it stays in the body. After treatment, doctors will do a bone marrow exam to see how the therapy affects the cancer.

    Treatment

    Your child will receive strong chemotherapy drugs to kill the cancer cells.

    Eligibility Overview

    • Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has come back or did not improve with chemotherapy
    • 21 years old or younger at enrollment
    • Able to swallow capsules
  3. PANAML   Quick View
    Sponsor St. Jude Children's Research Hospital
    Clinicaltrials.gov identifier NCT02676323
    Trial start date February 2016
    Estimated enrollment 36
    Study type Interventional/Therapeutic
    Study phase Phase 1/11
    Conditions Acute Myeloid Leukemia or Myelodysplastic Syndrome
    Ages Up to 21 years
    Principal investigator Jeffrey E. Rubnitz, MD, PhD
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss APNAML St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Jeffrey E. Rubnitz, MD, PhD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.