Childhood Acute Promyelocytic Leukemia (M3)Phase 1NCT00217412
Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia
A Phase 1 study testing vorinostat and isotretinoin in people with Childhood Acute Promyelocytic Leukemia (M3) and Childhood Atypical Teratoid/Rhabdoid Tumor, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Childhood Acute Promyelocytic Leukemia (M3), Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Burkitt Lymphoma
- What is being tested?
- vorinostat and isotretinoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Sep 2009
- 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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed* diagnosis of 1 of the following:
- Recurrent or refractory solid tumor or lymphoma (for patients in group 1)
- Measurable or evaluable disease
- Recurrent or refractory leukemia (for patients in group 2)
- Greater than 25% blasts in the bone marrow (i.e., M3 bone marrow)
- Active extramedullary disease allowed except leptomeningeal disease
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- Recurrent or refractory CNS tumor of 1 of the following types (for patients in group 3):
- Neuroblastoma
- Medulloblastoma/CNS primitive neuroectodermal tumor
- Atypical teratoid rhabdoid tumor
- No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
- No bone marrow involvement by disease (for patients in groups 1 and 3)
- No active CNS leukemia
- Performance status - Lansky 50-100% (for patients ≤ 10 years of age)
- Performance status - Karnofsky 60-100% (for patients > 10 years of age)
- Absolute neutrophil count ≥ 1,000/mm^3 (for solid tumor patients)
- Platelet count ≥ 100,000/mm^3* (for solid tumor patients) (20,000/mm^3** for leukemia patients)
- Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) (for solid tumor and leukemia patients)
- Triglycerides < 300 mg/dL (for patients in group 3)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 5 times ULN
- Albumin ≥ 2 g/dL
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
- Creatinine based on age as follows:
- No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
- No greater than 1.0 mg/dL (for patients 6 to 10 years of age)
- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)
- No greater than 1.5 mg/dL (for patients over 15 years of age)
- Negative dipstick for protein OR < 1,000 mg protein/24 hour urine collection (for patients in group 3)
- No evidence of gross hematuria (for patients in group 3)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Body surface area ≥ 0.5 m^2
- Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry
- Able to swallow whole capsules
- No uncontrolled infection
- Skin toxicity < grade 1 (for patients in group 3)
- Recovered from prior immunotherapy
- At least 7 days since prior hematopoietic growth factors
- At least 7 days since prior antineoplastic biologic agents
- At least 2 months since prior stem cell transplantation or rescue
- No evidence of active graft-versus-host disease
- No other concurrent biologic therapy or immunotherapy
- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
- No concurrent chemotherapy
- Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry
- No concurrent dexamethasone for antinausea or antiemetic therapy
- Recovered from prior radiotherapy
- At least 2 weeks since prior local, palliative, small-port radiotherapy
- At least 3 months since prior total-body irradiation, radiotherapy to the craniospinal area, or radiotherapy to ≥ 50% of the pelvis
- At least 6 weeks since other prior substantial radiotherapy to the bone marrow
- No concurrent radiotherapy
- At least 2 weeks since prior valproic acid
- No other concurrent investigational agents
- No other concurrent anticancer therapy
- No concurrent enzyme-inducing anticonvulsants
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase 1 Study of SAHA (NSC# 701852) in Pediatric Patients With Recurrent or Refractory Solid Tumors (Including Lymphomas) and Leukemia Followed by a Phase I Study of SAHA in Combination With 13-Cis-Retinoic Acid for Patients With Selected Recurrent/Refractory Solid Tumors
This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with recurrent or refractory solid tumors or lymphomas.
II. Determine the MTD of SAHA administered in combination with isotretinoin in young patients with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
III. Determine the tolerability of the solid tumor MTD of SAHA in young patients with recurrent or refractory leukemia.
IV. Determine the toxic effects of SAHA administered with or without isotretinoin in these patients.
- Determine the pharmacokinetics of this drug in these patients.
SECONDARY OBJECTIVES:
- Determine, preliminarily, the antitumor activity of SAHA administered with or without isotretinoin in these patients.
II. Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in these patients.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD.
Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.
Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD.
After completion of study treatment, patients are followed periodically.
- Conditions
- Childhood Acute Promyelocytic Leukemia (M3), Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma
- Being tested
- vorinostat, isotretinoin
- Medical subject headings
- Rhabdoid Tumor, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Leukemia, Myelomonocytic, Juvenile, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Dendritic Cell Sarcoma, Interdigitating, Medulloblastoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
isotretinoinDrug
Also called 13-CRA, Amnesteem, Cistane, Claravis
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD. Receives: Drug: vorinostat |
| Arm II | Experimental | Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD. Receives: Drug: vorinostat |
| Arm III | Experimental | Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD. Receives: Drug: vorinostat; Drug: isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities DLT graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: 28 days
Secondary outcomes (1)
The proportion of patients who demonstrate each polymorphism
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 2005
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Acute Promyelocytic Leukemia (M3)Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Maryam Fouladi, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00217412
- Sponsor's protocol ID
- NCI-2012-01821
- Other IDs
- NCI-2012-01821, CDR0000440999, COG-ADVL0416, NCI-06-C-0254, ADVL0416, ADVL0416
- Status last verified
- Apr 2013
- First submitted
- 20 Sep 2005
- Last updated
- 17 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of SAHA (NSC# 701852) in Pediatric Patients With Recurrent or Refractory Solid Tumors (Including Lymphomas) and Leukemia Followed by a Phase I Study of SAHA in Combination With 13-Cis-Retinoic Acid for Patients With Selected Recurrent/Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00217412
- Acronym / sponsor ID
- NCI-2012-01821
- Conditions
- Childhood Acute Promyelocytic Leukemia (M3), Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Burkitt Lymphoma, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2005
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 22 Sep 2005 (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 phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with recurrent or refractory solid tumors or lymphomas.
II. Determine the MTD of SAHA administered in combination with isotretinoin in young patients with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
III. Determine the tolerability of the solid tumor MTD of SAHA in young patients with recurrent or refractory leukemia.
IV. Determine the toxic effects of SAHA administered with or without isotretinoin in these patients.
- Determine the pharmacokinetics of this drug in these patients.
SECONDARY OBJECTIVES:
- Determine, preliminarily, the antitumor activity of SAHA administered with or without isotretinoin in these patients.
II. Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in these patients.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD.
Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.
Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: vorinostatGroup 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD. |
| Arm II | Experimental | Drug: vorinostatGroup 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD. |
| Arm III | Experimental | Drug: vorinostat, Drug: isotretinoinGroup 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (57 listed)
- Histologically confirmed* diagnosis of 1 of the following:
- No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
- No bone marrow involvement by disease (for patients in groups 1 and 3)
- No active CNS leukemia
- Performance status - Lansky 50-100% (for patients ≤ 10 years of age)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Arm I, Arm II, Arm III |
| isotretinoinAlso: 13-CRA, Amnesteem, Cistane, ClaravisGiven orally | Drug | Arm III |
Primary outcome
Maximum tolerated dose (MTD) defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities DLT graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: 28 days
1 secondary outcome
The proportion of patients who demonstrate each polymorphism
Time frame: Up to 4 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 17 Jun 2014.
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.
Maryam Fouladi principal investigator
Children's Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vorinostat and isotretinoin in people with Childhood Acute Promyelocytic Leukemia (M3) and Childhood Atypical Teratoid/Rhabdoid Tumor, run by National Cancer Institute (NCI) at 1 site 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 57 inclusion and 0 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 17 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Maximum tolerated dose (MTD) defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities DLT graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jun 2014.