A Study Of Panobinostat In Children With Refractory Hematologic Malignancies
NCT ID: NCT01321346
Last Updated: 2015-11-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
30 participants
INTERVENTIONAL
2011-03-31
Brief Summary
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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.
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Leukemia Patients
Patients with ALL and AML will be treated in one arm of the study.
Panobinostat
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.
Cytarabine
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.
Lymphoma Patients
Patients with NHL or HD will be treated in one arm of the study.
Panobinostat
Dose will be assigned at study entry. Patients will take panobinostat orally 3 times a week on a Monday, Wednesday, Friday schedule, every other week. Once course is 28 days (4 weeks). Patients will get 2 course and may receive up to 8 courses of therapy.
Interventions
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Panobinostat
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.
Cytarabine
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.
Panobinostat
Dose will be assigned at study entry. Patients will take panobinostat orally 3 times a week on a Monday, Wednesday, Friday schedule, every other week. Once course is 28 days (4 weeks). Patients will get 2 course and may receive up to 8 courses of therapy.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have one of the following:
1. 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.
2. 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.
3. 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.
1. Patients with AML must have had at least 2 prior therapeutic attempts including frontline induction.
2. Patients with ALL must have had at least 3 prior therapeutic attempts including frontline induction.
3. Radiotherapy: At least 28 days must have elapsed since and radiation therapy.
4. 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.
5. 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®).
6. 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.
7. Prior HSCT for Hodgkin's Lymphoma: Patients with Hodgkin's lymphoma must have had prior attempt at autologous HSCT.
* Renal and Hepatic Function
1. Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2.
* Pediatric Population (age \<18): Calculated creatinine clearance ≥ 90 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR)
* Adult Population (age \>18): Serum creatinine \<1.0 mg/dL; if serum creatinine \>1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \>60 mL/min/1.73 m2
2. Patient's ALT must be \< 5 x institutional upper limit of norm ULN.
3. Patient's total bilirubin must be ≤ 1.5 x ULN.
* Cardiac Function
a. Patient must have a shortening fraction ≥ 29% or an ejection fraction ≥ 40% by ECHO/MUGA.
* Reproductive Function
1. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
2. Female patients with infants must agree not to breastfeed their infants while on this study.
3. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
Exclusion Criteria
* 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
1. Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat.
2. 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:
1. 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).
2. Any history of ventricular fibrillation or torsade de pointes.
3. Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
4. Screening ECG with a QTc \> 450 msec.
5. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.
6. Right bundle branch block + left anterior hemiblock (bifascicular block).
7. Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug.
8. Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
9. Patients with leukemia must not be known to be refractory to red blood cell or platelet transfusions.
8 Years
21 Years
ALL
No
Sponsors
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Novartis
INDUSTRY
Therapeutic Advances in Childhood Leukemia Consortium
OTHER
Responsible Party
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Principal Investigators
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Julio Barredo, MD
Role: STUDY_CHAIR
University of Miami
Locations
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Childrens Hospital Los Angeles
Los Angeles, California, United States
UCSF School of Medicine
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, 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, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States
New York University Medical Center
New York, New York, United States
Children's Hospital New York-Presbyterian
New York, New York, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, 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, 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, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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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.
Related Links
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TACL Consortium Web Site
Other Identifiers
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T2009-012
Identifier Type: -
Identifier Source: org_study_id