NeuroblastomaPhase 1/2NCT01592045
ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma
A Phase 1/2 study testing ch14.18 -NCI, ch14.18-UTC and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in people with Neuroblastoma, run by United Therapeutics at 13 sites in United States.
Trial summary
The purpose of this study is to compare the pharmacokinetics (blood levels) and safety of chimeric (ch) 14.18 manufactured by two independent drug makers (United Therapeutics [UTC] or the National Cancer Institute [NCI]). Read more about this study
- Who is it for?
- Ages Up to 8 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- ch14.18 -NCI, ch14.18-UTC and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 13 sitesUnited States
- Study dates
- Aug 2012to Jun 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 8 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of high-risk neuroblastoma
- 8 years of age or younger at diagnosis of high-risk neuroblastoma
- Patients must have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy
- Radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor
- Must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows:
- No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy
Show all 12Show fewer
- Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible
- No more than 12 months from starting the first induction chemotherapy after diagnosis to the date of ASCT
- For patients who became high-risk neuroblastoma after initial non-high risk disease, the 12 months period should start from the date of induction therapy for high-risk neuroblastoma to the date of ASCT
- No progressive disease at time of registration except for protocol-specified bone marrow response
- Adequate hematological, renal, hepatic, pulmonary and cardiac function
- CNS toxicity < Grade 2
Who cannot join
- Prior anti-GD2 antibody therapy
- Prior vaccine therapy for neuroblastoma
- Concurrent anti-cancer or immunosuppressive therapy
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of Michigan C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Chicago
Chicago, Illinois, 60637
Duke University Medical Center
Durham, North Carolina, 27710
Cook Children's Medical Center
Fort Worth, Texas, 76104
Children's Mercy Hospital (Kansas)
Kansas City, Missouri, 64108
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63310
About this study
Official title: A Comparative Pharmacokinetic and Safety Study of Chimeric Monoclonal Antibody ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-2 (IL-2) and Isotretinoin in High Risk Neuroblastoma Patients Following Myeloablative Therapy
The purpose of this study is to compare the pharmacokinetics (blood levels) and safety of chimeric (ch) 14.18 manufactured by two independent drug makers (United Therapeutics [UTC] or the National Cancer Institute [NCI]).
Read the detailed description
This is a multi-center, randomized, open-label, two-sequence, cross-over study for eligible subjects with high-risk neuroblastoma to assess the comparability of ch14.18 manufactured with UTC drug product and ch14.18 manufactured with NCI drug product. Subjects will be randomly allocated to receive ch14.18 manufactured by UTC or NCI during Courses 1 and 2 followed by ch14.18 manufactured by other manufacturer (UTC or NCI) during Courses 3, 4, and 5.
- Conditions
- Neuroblastoma
- Being tested
- ch14.18 -NCI, ch14.18-UTC, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Aldesleukin (IL-2), Isotretinoin
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ch14.18 -NCIBiological
25 mg/m^2/day IV for four consecutive days
ch14.18-UTCBiological
17.5 mg/m^2/day IV for four consecutive days
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)Biological
GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.
Aldesleukin (IL-2)Biological
Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4.
IsotretinoinDrug
Also called 13-cis-retinoic acid
Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows:
If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily).
If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Experimental | UTC ch14.18 for two courses and NCI ch14.18 for three courses Receives: Biological: ch14.18 -NCI; Biological: ch14.18-UTC; Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF); Biological: Aldesleukin (IL-2); Drug: Isotretinoin |
| Sequence 2 | Experimental | NCI ch14.18 for two courses and UTC ch14.18 for three courses Receives: Biological: ch14.18 -NCI; Biological: ch14.18-UTC; Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF); Biological: Aldesleukin (IL-2); Drug: Isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration Curve (AUC)
Twenty-two PK samples will be obtained at the following timepoints:
Courses 1 and 3:
Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample
Courses 2 and 4:
Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Measured: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Peak Plasma Concentration (Cmax)
Twenty-two PK samples will be obtained at the following timepoints:
Courses 1 and 3:
Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample
Courses 2 and 4:
Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Measured: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2012 (estimated)
- Study startAug 2012
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeuroblastomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Araz Marachelian, MD, Study chair, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01592045
- Sponsor's protocol ID
- DIV-NB-201
- Status last verified
- Aug 2015
- First submitted
- 30 Apr 2012
- Last updated
- 23 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Pharmacokinetic and Safety Study of Chimeric Monoclonal Antibody ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-2 (IL-2) and Isotretinoin in High Risk Neuroblastoma Patients Following Myeloablative Therapy
- ClinicalTrials.gov ID
- NCT01592045
- Acronym / sponsor ID
- DIV-NB-201
- Conditions
- Neuroblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 4 May 2012 (estimated)
- Results
- Posted 23 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the pharmacokinetics (blood levels) and safety of chimeric (ch) 14.18 manufactured by two independent drug makers (United Therapeutics [UTC] or the National Cancer Institute [NCI]).
Detailed description
This is a multi-center, randomized, open-label, two-sequence, cross-over study for eligible subjects with high-risk neuroblastoma to assess the comparability of ch14.18 manufactured with UTC drug product and ch14.18 manufactured with NCI drug product. Subjects will be randomly allocated to receive ch14.18 manufactured by UTC or NCI during Courses 1 and 2 followed by ch14.18 manufactured by other manufacturer (UTC or NCI) during Courses 3, 4, and 5.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Biological: ch14.18 -NCI, Biological: ch14.18-UTC, Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Biological: Aldesleukin (IL-2), Drug: IsotretinoinUTC ch14.18 for two courses and NCI ch14.18 for three courses |
| Sequence 2 | Experimental | Biological: ch14.18 -NCI, Biological: ch14.18-UTC, Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Biological: Aldesleukin (IL-2), Drug: IsotretinoinNCI ch14.18 for two courses and UTC ch14.18 for three courses |
Who may qualify
- Ages
- Up to 8 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Diagnosis of high-risk neuroblastoma
- 8 years of age or younger at diagnosis of high-risk neuroblastoma
- Patients must have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy
- Must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows:
- Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible
Key exclusion criteria (3 listed)
- Prior anti-GD2 antibody therapy
- Prior vaccine therapy for neuroblastoma
- Concurrent anti-cancer or immunosuppressive therapy
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 |
|---|---|---|
| ch14.18 -NCI25 mg/m^2/day IV for four consecutive days | Biological | Sequence 1, Sequence 2 |
| ch14.18-UTC17.5 mg/m^2/day IV for four consecutive days | Biological | Sequence 1, Sequence 2 |
| Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5. | Biological | Sequence 1, Sequence 2 |
| Aldesleukin (IL-2)Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4. | Biological | Sequence 1, Sequence 2 |
| IsotretinoinAlso: 13-cis-retinoic acidIsotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows: If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily). If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily). | Drug | Sequence 1, Sequence 2 |
Primary outcome
Area Under the Plasma Concentration Curve (AUC)
Time frame: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Peak Plasma Concentration (Cmax)
Time frame: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment
Twenty-two PK samples will be obtained at the following timepoints: Courses 1 and 3: Day: 0 Days: 3, 4, 5 and 6: post ch14.18 Days 7:10 to 14 hours post ch14.18 Days 9 to 11: Single sample Days 14 to 17: Single sample Courses 2 and 4: Day 0: Pre-IL-2 Day 7: Pre-ch14.18 Day 10 (Course 4 only): Post ch14.18 End of Treatment: Within 2 weeks post isotretinoin
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Araz Marachelian, MD study chair
Children's Hospital Los Angeles
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ch14.18 -NCI, ch14.18-UTC and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in people with Neuroblastoma, run by United Therapeutics at 13 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 12 inclusion and 3 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 23 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Plasma Concentration Curve (AUC) (time frame: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment). 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?
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 23 Sep 2015.