Lymphoblastic Leukemia, Acute, ChildhoodPhase 1NCT01321346
A Study Of Panobinostat In Children With Refractory Hematologic Malignancies
A Phase 1 study testing Panobinostat and Cytarabine in people with Lymphoblastic Leukemia, Acute, Childhood and Myelogenous Leukemia, Acute, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 20 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 8 to 21 years
- Conditions the study is for
- Lymphoblastic Leukemia, Acute, Childhood, Myelogenous Leukemia, Acute, Childhood, Hodgkin's Disease
- What is being tested?
- Panobinostat and Cytarabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 20 sitesUnited States
- Study dates
- Mar 2011to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
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- 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.
- Prior HSCT for Hodgkin's Lymphoma: Patients with Hodgkin's lymphoma must have had prior attempt at autologous HSCT.
- Renal and Hepatic Function
- 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
- Patient's ALT must be < 5 x institutional upper limit of norm ULN.
- Patient's total bilirubin must be ≤ 1.5 x ULN.
- Cardiac Function
- Patient must have a shortening fraction ≥ 29% or an ejection fraction ≥ 40% by ECHO/MUGA.
- Reproductive Function
- Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
Who cannot join
- 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.
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- 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.
- Cardiac Exclusion Criteria:
- 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.
- 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.
- Right bundle branch block + left anterior hemiblock (bifascicular block).
- Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug.
- 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).
- Patients with leukemia must not be known to be refractory to red blood cell or platelet transfusions.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-0914
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia
Dana Farber
Boston, Massachusetts
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, 28203
Lurie Children's Hospital
Chicago, Illinois
Rainbow Babies
Cleveland, Ohio
Nationwide Childrens Hospital
Columbus, Ohio
Childrens Hospital Los Angeles
Los Angeles, California, 90027
St. Jude
Memphis, Tennessee, 38105-3678
University of Miami Cancer Center
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404-4597
Vanderbilt Children's Hospital
Nashville, Tennessee
New York University Medical Center
New York, New York, 10016
Children's Hospital New York-Presbyterian
New York, New York, 10032
Oregon Health and Science University
Portland, Oregon
Primary Children's
Salt Lake City, Utah
UCSF School of Medicine
San Francisco, California, 94143-0106
Seattle Children's Hospital
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia
About this study
Official title: A Phase I Dose Finding Study Of Panobinostat In Children With Refractory Hematologic Malignancies
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.
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Myelogenous Leukemia, Acute, Childhood, Hodgkin's Disease, Non-Hodgkin's Lymphoma
- Being tested
- Panobinostat, Cytarabine
- Keywords
- Relapse, Lymphoblastic, Leukemia, Panobinostat, LBH589, Refractory, Hodgkin's, Non-Hodgkin's Lymphoma, Lymphoma, Myelogenous, Acute, Childhood, Pediatric, ALL, AML, NHL, HD
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Hodgkin Disease, Lymphoma, Non-Hodgkin, Recurrence, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
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.
CytarabineDrug
Also called Ara-C, cytosine arabinoside, Cytosar
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.
PanobinostatDrug
Also called LBH589
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.
| Study group | Role | What they receive |
|---|---|---|
| Leukemia Patients | Experimental | Patients with ALL and AML will be treated in one arm of the study. Receives: Drug: Panobinostat; Drug: Cytarabine |
| Lymphoma Patients | Experimental | Patients with NHL or HD will be treated in one arm of the study. Receives: Drug: Panobinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
To learn what kind of side effects panobinostat can cause when taken by children with relapsed ALL, AML, HD or NHL.
Measured: 8 weeks
Secondary outcomes (3)
To determine whether panobinostat is a beneficial treatment for ALL, AML, HD or NHL.
Measured: 8 weeks
To test the amount of panobinostat in the patient's blood and spinal fluid after taking panobinostat.
Measured: 3 years
To test samples of cancer cells to see if they have chemicals that affect the way panobinostat works.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoblastic Leukemia, Acute, ChildhoodStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Julio Barredo, MD, Study chair, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01321346
- Sponsor's protocol ID
- T2009-012
- Status last verified
- Nov 2015
- First submitted
- 21 Mar 2011
- Last updated
- 24 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32338562
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Finding Study Of Panobinostat In Children With Refractory Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01321346
- Acronym / sponsor ID
- T2009-012
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Myelogenous Leukemia, Acute, Childhood, Hodgkin's Disease, Non-Hodgkin's Lymphoma
- Keywords
- Relapse, Lymphoblastic, Leukemia, Panobinostat, LBH589, Refractory, Hodgkin's, Non-Hodgkin's Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia ConsortiumUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2011
- Primary completion
- Oct 2015 (actual)
- First posted
- 23 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Leukemia Patients | Experimental | Drug: Panobinostat, Drug: CytarabinePatients with ALL and AML will be treated in one arm of the study. |
| Lymphoma Patients | Experimental | Drug: PanobinostatPatients with NHL or HD will be treated in one arm of the study. |
Who may qualify
- Ages
- 8 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Patients must be ≤ 21 years of age at the time of enrollment.
- Patients must have one of the following:
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanobinostatAlso: LBH589Dose 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. | Drug | Leukemia Patients |
| CytarabineAlso: Ara-C, cytosine arabinoside, CytosarAll 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. | Drug | Leukemia Patients |
| PanobinostatAlso: LBH589Dose 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. | Drug | Lymphoma Patients |
Primary outcome
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.
Time frame: 8 weeks
To learn what kind of side effects panobinostat can cause when taken by children with relapsed ALL, AML, HD or NHL.
Time frame: 8 weeks
3 secondary outcomes
To determine whether panobinostat is a beneficial treatment for ALL, AML, HD or NHL.
Time frame: 8 weeks
To test the amount of panobinostat in the patient's blood and spinal fluid after taking panobinostat.
Time frame: 3 years
To test samples of cancer cells to see if they have chemicals that affect the way panobinostat works.
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2015.
- Derived from this study: PubMed 32338562Goldberg 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.
- TACL Consortium Web SiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio Barredo, MD study chair
University of Miami
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Panobinostat and Cytarabine in people with Lymphoblastic Leukemia, Acute, Childhood and Myelogenous Leukemia, Acute, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01321346, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2015.