Acute Myelogenous LeukemiaPhase 1NCT01187810
Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL
A Phase 1 study testing Fenretinide, Cytarabine and Methotrexate in people with Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia, run by South Plains Oncology Consortium at 2 sites in United States.
Trial summary
The purposee of this study is to determine the safety and dosing of Fenretinide when given continuously for 5 days, every 3 weeks, in pediatric patients with recurrent and/or resistant acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and non-Hodgkin's lymphoma (NHL). Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma
- What is being tested?
- Fenretinide, Cytarabine and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2010to Apr 2018
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosed with relapsed or refractory ALL, AML, or NHL
- Must have had two or more therapeutic attempts for treating/curing disease
- Must have fully recoved from acute toxic effects of all prior therapy
- Karnofsky of greater than 50% for older than 10 years of age and Lansky greater than 50% for younger than 10 years.
Who cannot join
- Grade 2 Pruritus or Rash (all forms)
- Grade 3 Dry Skin that is refractory to topical medical management
- Cardiac Fractional Shortening < 27% on echocardiogram
- Left Ventricular Ejection Fraction < 45% on echocardiogram
- Known allergy to egg products or soy bean oil
- Renal, Liver, and Pancreatic function:
Show all 12Show fewer
- serum creatinine > 1.5X ULN
- direct bilirubin > 1.5X ULN
- ALT or AST > 2.5X ULN
- Serum trigylcerides > 2.5X ULN for age
- Lipase > 1.5X ULN for age
- History of pancreatitis
Trial locations and contacts
2 sites in 1 country.
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
About this study
Official title: A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children With Recurrent or Resistant Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), and Non-Hodgkin's Lymphoma (NHL) IND #70,058"
The purposee of this study is to determine the safety and dosing of Fenretinide when given continuously for 5 days, every 3 weeks, in pediatric patients with recurrent and/or resistant acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and non-Hodgkin's lymphoma (NHL).
Read the detailed description
Fenretinide is a cytotoxic retinoid that has activity against a variety of cell lines in vitro in a dose-related manner. The exact mechanism of fenretinide cytotoxicity in leukemia and lymphoma cell lines is not known, but may include the de novo ceramide synthesis of ceramides and the generation of reactive oxygen species. The malignancy-specific nature of fenretinide-induced ceramides suggests that combinations of the drug with other ceramide modulating agents may have a favorable therapeutic index.
In this study, the primary aims are to define the maximum tolerated dose, toxicity profile, and pharmacokinetics of IV fenretinide when given continuously in pediatric patients with ALL, AML, and NHL. The drug will be administered via a central venous or percutaneous indwelling central catheter in an inpatient hospital setting.
- Being tested
- Fenretinide, Cytarabine, Methotrexate
- Keywords
- leukemia,lymphoma
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenretinideDrug
Also called N-(4-hydroxyphenyl) retinamide, 4-HPR
925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis.
CytarabineDrug
Also called Ara-C, Cytosine Arabinoside, Cytosar
dosing depending on age - will be administed intrathecally for all CNS negative subjects on day 0 and 15 of course 1, then on day 8 of each remaining cycle for CNS negative AML. For CNS positive ALL, NHL, and AML, will be administered alone on day 0 for and in combination with methotrexate and hydrocortisone on day 8, 15, 22 of cycle 1 and repeated on day 8 of each remaining cycle
MethotrexateDrug
Also called MTX, Amethopterin
Dose depends on subject age - for CNS positive patients, will be given in combination with cytarabine and hydrocortisone on days 8, 15, and 22 during course 1. For courses 2-6, will be administered intrathecally on day 8 for CNS negative ALL and NHL. For patients who are CNS positive, it will be given in combination with cytarabine and hydrocortisone on day 8 of courses 2-6.
| Study group | Role | What they receive |
|---|---|---|
| Combination of Fenretinide, Cytarabine, and Methotrexate | Experimental | IV for 7 days for each 21 day cycle Receives: Drug: Fenretinide; Drug: Cytarabine; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine maximum tolerated dose
Measured: end of study
Define systemic toxicities
Measured: end of study
Determine plasma pharmacokinetics
Measured: end of study
Secondary outcomes (2)
Determine the response rate to IV Fenretinide
Measured: end of study
Determine bioavailability of fenretinide and metabolites
To determine the bioavailability to cancer or peripheral blood mononuclear cells (PBMC) cells of fenretinide and metabolites delivered/obtained as an intravenous emulsion. To determine alterations to sphingolipid levels in PBMC and/or circulating leukemia blasts induced by fenretinide.
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionApr 2018
- Study completionApr 2018
Why it stopped: drug supply
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- South Plains Oncology Consortium
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Anna R Franklin, MD, Study chair, M.D. Anderson Cancer CenterBarry J Maurer, MD, PhD, Study chair, Texas Tech University Health Sciences CenterShengping Yang, PhD, Study director, Texas Tech University Health Sciences CenterMin Kang, PharmD, Study director, Texas Tech University Health Sciences CenterPatrick Reynolds, MD, PhD, Study director, Texas Tech University Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01187810
- Sponsor's protocol ID
- SPOC2008-01
- Status last verified
- Mar 2022
- First submitted
- 23 Aug 2010
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children With Recurrent or Resistant Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), and Non-Hodgkin's Lymphoma (NHL) IND #70,058"
- ClinicalTrials.gov ID
- NCT01187810
- Acronym / sponsor ID
- SPOC2008-01
- Keywords
- leukemia,lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: drug supply
- Enrolment
- 3 participants (actual)
- Lead sponsor
- South Plains Oncology ConsortiumResearch network
- Study start
- Aug 2010
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 24 Aug 2010 (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.
The purposee of this study is to determine the safety and dosing of Fenretinide when given continuously for 5 days, every 3 weeks, in pediatric patients with recurrent and/or resistant acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and non-Hodgkin's lymphoma (NHL).
Detailed description
Fenretinide is a cytotoxic retinoid that has activity against a variety of cell lines in vitro in a dose-related manner. The exact mechanism of fenretinide cytotoxicity in leukemia and lymphoma cell lines is not known, but may include the de novo ceramide synthesis of ceramides and the generation of reactive oxygen species. The malignancy-specific nature of fenretinide-induced ceramides suggests that combinations of the drug with other ceramide modulating agents may have a favorable therapeutic index.
In this study, the primary aims are to define the maximum tolerated dose, toxicity profile, and pharmacokinetics of IV fenretinide when given continuously in pediatric patients with ALL, AML, and NHL. The drug will be administered via a central venous or percutaneous indwelling central catheter in an inpatient hospital setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination of Fenretinide, Cytarabine, and Methotrexate | Experimental | Drug: Fenretinide, Drug: Cytarabine, Drug: MethotrexateIV for 7 days for each 21 day cycle |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Diagnosed with relapsed or refractory ALL, AML, or NHL
- Must have had two or more therapeutic attempts for treating/curing disease
- Must have fully recoved from acute toxic effects of all prior therapy
- Karnofsky of greater than 50% for older than 10 years of age and Lansky greater than 50% for younger than 10 years.
Key exclusion criteria (12 listed)
- Grade 2 Pruritus or Rash (all forms)
- Grade 3 Dry Skin that is refractory to topical medical management
- Cardiac Fractional Shortening < 27% on echocardiogram
- Left Ventricular Ejection Fraction < 45% on echocardiogram
- Known allergy to egg products or soy bean oil
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 |
|---|---|---|
| FenretinideAlso: N-(4-hydroxyphenyl) retinamide, 4-HPR925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis. | Drug | Combination of Fenretinide, Cytarabine, and Methotrexate |
| CytarabineAlso: Ara-C, Cytosine Arabinoside, Cytosardosing depending on age - will be administed intrathecally for all CNS negative subjects on day 0 and 15 of course 1, then on day 8 of each remaining cycle for CNS negative AML. For CNS positive ALL, NHL, and AML, will be administered alone on day 0 for and in combination with methotrexate and hydrocortisone on day 8, 15, 22 of cycle 1 and repeated on day 8 of each remaining cycle | Drug | Combination of Fenretinide, Cytarabine, and Methotrexate |
| MethotrexateAlso: MTX, AmethopterinDose depends on subject age - for CNS positive patients, will be given in combination with cytarabine and hydrocortisone on days 8, 15, and 22 during course 1. For courses 2-6, will be administered intrathecally on day 8 for CNS negative ALL and NHL. For patients who are CNS positive, it will be given in combination with cytarabine and hydrocortisone on day 8 of courses 2-6. | Drug | Combination of Fenretinide, Cytarabine, and Methotrexate |
Primary outcome
Determine maximum tolerated dose
Time frame: end of study
Define systemic toxicities
Time frame: end of study
Determine plasma pharmacokinetics
Time frame: end of study
2 secondary outcomes
Determine the response rate to IV Fenretinide
Time frame: end of study
Determine bioavailability of fenretinide and metabolites
Time frame: end of study
Results and safety
The study was stopped early (reason given: drug supply). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Individual participant dataSharing planned: Undecided
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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.
Anna R Franklin, MD study chair
M.D. Anderson Cancer Center
Barry J Maurer, MD, PhD study chair
Texas Tech University Health Sciences Center
Shengping Yang, PhD study director
Texas Tech University Health Sciences Center
2 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 Fenretinide, Cytarabine and Methotrexate in people with Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia, run by South Plains Oncology Consortium at 2 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 4 inclusion and 12 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: stopped early, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 was stopped early (reason given: drug supply). Results are not available in the source record.
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?
Determine maximum tolerated dose (time frame: end of study). The study lists 3 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 31 Mar 2022.