A Study Of Panobinostat In Children With Refractory Hematologic Malignancies
A Phase I Dose Finding Study Of Panobinostat In Children With Refractory Hematologic Malignancies
1 other identifier
interventional
30
1 country
20
Brief Summary
This study is for patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Hodgkin's Disease (HD) or Non-Hodgkin's Lymphoma (NHL). Panobinostat is a new drug that is considered investigational because it has not been approved in the United States by the Food and Drug Administration (FDA), or in any other country. Panobinostat is a histone deacetylase inhibitor (HDACi) and interferes with gene expression found in cells causing them to stop growing or die. Panobinostat has been used in several hundred adults who had leukemia, HD, NHL and other solid tumors. Panobinostat has not been given to children. This is a phase I study. In a phase I study, drugs are tested to the highest dose that can be safely given. Drugs are given at gradually increasing dosages until there are unacceptable side effects. The goal of the Phase I study is to find out the dose of panobinostat that can be safely given to children with relapsed ALL, AML, HD and NHL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2011
CompletedFirst Submitted
Initial submission to the registry
March 21, 2011
CompletedFirst Posted
Study publicly available on registry
March 23, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2015
CompletedNovember 24, 2015
November 1, 2015
4.6 years
March 21, 2011
November 20, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To find the highest dose of oral panobinostat that can be given to patients with relapsed AML, HD or NHL without causing severe side effects.
8 weeks
To learn what kind of side effects panobinostat can cause when taken by children with relapsed ALL, AML, HD or NHL.
8 weeks
Secondary Outcomes (3)
To determine whether panobinostat is a beneficial treatment for ALL, AML, HD or NHL.
8 weeks
To test the amount of panobinostat in the patient's blood and spinal fluid after taking panobinostat.
3 years
To test samples of cancer cells to see if they have chemicals that affect the way panobinostat works.
3 years
Study Arms (2)
Leukemia Patients
EXPERIMENTALPatients with ALL and AML will be treated in one arm of the study.
Lymphoma Patients
EXPERIMENTALPatients with NHL or HD will be treated in one arm of the study.
Interventions
Dose will be assigned at study entry. Patients will take panobinostat orally 3 times a week given on a Monday, Wednesday, Friday schedule, every week. One course is 28 days (4 weeks). Patients will get 2 courses and may receive up to 8 courses total.
All patients will receive 70 mg of intrathecal cytarabine on day "0" of course 1. The day "0" dose must be given at least 24 hours prior to initiation of panobinostat. Omit the day "0" dose of intrathecal cytarabine if the patient received intrathecal therapy within 72 hours of treatment. All patients will receive 70 mg of intrathecal cytarabine on day "29" of course 1-8 in conjunction with their disease evaluation.
Eligibility Criteria
You may qualify if:
- Patients must be ≤ 21 years of age at the time of enrollment.
- Patients must have one of the following:
- Patient must have relapsed/refractory acute myelogenous leukemia (AML) with ≥ 5% blast in the bone marrow or biopsy confirmed chloroma. Patient may have CNS 1, 2 or 3 disease. Isolated CNS relapse is not eligible.
- Patient must have relapsed/refractory acute lymphoblastic leukemia (ALL) with ≥ 5 blasts in the bone marrow or biopsy confirmed extramedullary disease. Patient may have CNS 1, 2 or 3 disease. Isolated CNS relapse is not eligible.
- Patient must have relapsed or refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease. Patients must have CNS 1 disease. Patient must have histologic verification of disease at original diagnosis. Patient must have measurable disease documented by clinical or radiographic criteria or bone marrow disease present at study entry.
- Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients less than or equal to 16 years of age. (See Appendix I for Performance Scales).
- Patient must have a life expectancy of 8 weeks.
- PRIOR THERAPY Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Patients with AML must have had at least 2 prior therapeutic attempts including frontline induction.
- Patients with ALL must have had at least 3 prior therapeutic attempts including frontline induction.
- Radiotherapy: At least 28 days must have elapsed since and radiation therapy.
- Hematopoietic Stem Cell Transplant:
- Patients who have had previous allogeneic HSCT must have grade I or less of Graft-versus-Host Disease (GVHD) and have not received immunosuppressive medication for at least 90 days.
- Hematopoietic grow factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
- Biologic/Immunologic (anti-neoplastic) therapy: It must be at least 28 days since the completion of therapy with a biologic/immunologic agent such as a monoclonal antibody prior to study enrollment and at least 28 days since non-study chemotherapy has been administered, excluding CNS directed therapy as described in Section 4.1.
- +13 more criteria
You may not qualify if:
- Patients will be excluded if they are unable to swallow capsules whole.
- Patients will be excluded if they have received previous therapy with HDAC, DAC, HSP90 inhibitors or valproic acid anticancer therapy. Valproic acid therapy is not allowed for any reason while on this study.
- AML patients who are candidates for allogeneic stem cell transplant are excluded.
- Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
- Gastrointestinal Function
- Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat.
- Patients with diarrhea \> CTCAE grade 2.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period, excluding CNS directed therapy upfront for AML patients and continuing for CNS positive patients as described in Section 4.1. Cyto-reduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start or protocol therapy.
- Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required.
- Patients will be excluded if these meet any of the following:
- History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the study chair prior to enrollment).
- Any history of ventricular fibrillation or torsade de pointes.
- Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
- Screening ECG with a QTc \> 450 msec.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Therapeutic Advances in Childhood Leukemia Consortiumlead
- Novartiscollaborator
Study Sites (20)
Childrens Hospital Los Angeles
Los Angeles, California, 90027, United States
UCSF School of Medicine
San Francisco, California, 94143-0106, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, 33136, United States
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States
Lurie Children's Hospital
Chicago, Illinois, United States
Dana Farber
Boston, Massachusetts, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-0914, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404-4597, United States
New York University Medical Center
New York, New York, 10016, United States
Children's Hospital New York-Presbyterian
New York, New York, 10032, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, 28203, United States
Rainbow Babies
Cleveland, Ohio, United States
Nationwide Childrens Hospital
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
St. Jude
Memphis, Tennessee, 38105-3678, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
Primary Children's
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Related Publications (1)
Goldberg J, Sulis ML, Bender J, Jeha S, Gardner R, Pollard J, Aquino V, Laetsch T, Winick N, Fu C, Marcus L, Sun W, Verma A, Burke M, Ho P, Manley T, Mody R, Tcheng W, Thomson B, Park J, Sposto R, Messinger Y, Hijiya N, Gaynon P, Barredo J. A phase I study of panobinostat in children with relapsed and refractory hematologic malignancies. Pediatr Hematol Oncol. 2020 Sep;37(6):465-474. doi: 10.1080/08880018.2020.1752869. Epub 2020 Apr 27.
PMID: 32338562DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Julio Barredo, MD
University of Miami
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 21, 2011
First Posted
March 23, 2011
Study Start
March 1, 2011
Primary Completion
October 1, 2015
Last Updated
November 24, 2015
Record last verified: 2015-11