Chronic Myeloproliferative DisordersPhase 1NCT00104923
Fenretinide in Treating Patients With Refractory or Relapsed Hematologic Cancer
A Phase 1 study testing fenretinide in people with Chronic Myeloproliferative Disorders and Leukemia, run by California Cancer Consortium at 4 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fenretinide in a different way may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- fenretinide
- Type of treatment
- Injection or infusion
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2005to Apr 2017
- 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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:
- Non-Hodgkin's lymphoma (NHL)
- Hodgkin's lymphoma
- Multiple myeloma
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Chronic hematologic malignancy with a poor prognosis (e.g., failed 3 prior standard therapies), including any of the following:
- Chronic lymphocytic leukemia
- Chronic myelogenous leukemia
- Indolent NHL
- Myeloproliferative disorders
- Refractory or relapsed disease, as defined by 1 of the following:
- Resistant to standard therapy for refractory or relapsed disease
- Progressed after standard therapy for advanced disease
- No effective treatment exists
- Measurable or evaluable disease
- No active CNS disease
- Previously treated leptomeningeal disease or brain metastases allowed provided there is no evidence of remaining cancer by positron-emission tomography, MRI, or spinal fluid cytology
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 3 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3 (unless due to bone marrow involvement of disease)
- Platelet count ≥ 75,000/mm^3 (unless due to bone marrow involvement of disease)
- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
- No coagulation disorders
Hepatic
- AST and ALT < 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastasis)
- Bilirubin ≤ 1.5 times ULN
Renal
- Creatinine ≤ 1.5 times ULN
Cardiovascular
- No major cardiovascular disease
Pulmonary
- No major respiratory disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception prior to study entry, during study, and for at least 6 months after study participation
- No uncontrolled systemic infection
- No uncontrolled hypertriglyceridemia (i.e., triglyceride level > 500 mg/dL)
- No known HIV positivity
- No known allergy to egg products
- No known familial hyperlipidemia disorders
- No previously undiscovered hypertriglyceridemia
- No poorly controlled diabetes
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 2 weeks since prior chemotherapy except hydroxyurea
- No concurrent hydroxyurea during study drug administration
- No other concurrent anticancer chemotherapy
Endocrine therapy
- No concurrent hormone-ablative agents
- No concurrent steroids
- No concurrent tamoxifen or any of its analogues
Radiotherapy
- No prior cranial radiotherapy
- More than 2 weeks since prior radiotherapy
Surgery
- More than 20 days since prior surgery except for biopsy
Other
- Recovered from all prior therapy
- More than 2 weeks since prior investigational agents
- No other concurrent investigational agents
- No other concurrent antineoplastic therapy
- No other concurrent antioxidants
- No concurrent herbal or other alternative therapies
- No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)
- Standard dose multivitamin allowed
- No other concurrent medications that may act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein or multidrug resistance protein 1 (MRP1) drug/lipid transporters, including any of the following:
- Cyclosporine or any of its analogues
- Verapamil
- Ketoconazole
- Chlorpromazine
- Mifepristone
- Indomethacin
- Sulfinpyrazone
- No concurrent medications that may cause pseudotumor cerebri, including any of the following:
- Tetracycline
- Nalidixic acid
- Nitrofurantoin
- Phenytoin
- Sulfonamides
- Lithium
- Amiodarone
- No concurrent medication to control hypertriglyceridemia
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90089-9181
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, 79410-1894
About this study
Official title: Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fenretinide in a different way may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating patients with refractory or relapsed hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of intravenous emulsified fenretinide in patients with refractory or relapsed hematologic malignancies.
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics and in vivo activity of this drug in these patients.
- Determine, preliminarily, disease or tumor response in patients treated with this drug.
OUTLINE: This is a pilot, dose-escalation, multicenter study.
Patients receive emulsified fenretinide IV continuously over 5 days. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.
Cohorts of 1 patient receive accelerated escalating doses of fenretinide until 2 patients experience moderate toxicity (cumulative across all dose levels) OR 1 patient experiences dose-limiting toxicity (DLT). After completion of the accelerated dose-escalation portion, the standard dose-escalation portion begins. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. At least 6 patients are treated at the MTD. An additional 12 patients are treated at the MTD.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- Being tested
- fenretinide
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent small lymphocytic lymphoma, recurrent mantle cell lymphoma, Waldenstrom macroglobulinemia, adult grade III lymphomatoid granulomatosis, recurrent adult grade III lymphomatoid granulomatosis, secondary acute myeloid leukemia, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, refractory chronic lymphocytic leukemia, recurrent adult lymphoblastic lymphoma, recurrent adult Hodgkin lymphoma, refractory multiple myeloma
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Congenital Abnormalities, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fenretinideDrug
Current dose level as an IV continuous infusion via central line over 5 days. Cycle is repeated every 3 weeks for up to 6 cycles
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of fenretinide
Measured: participants will be followed for the duration of cycle 1, which is expected to be 3 weeks.
To describe the toxicities of fenretinide
Measured: participants will be followed for the duration of treatment, which is expected to be 18 weeks or less
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2005 (estimated)
- Study startFeb 2005
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloproliferative DisordersStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- California Cancer Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ann Mohrbacher, MD, Study chair, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00104923
- Sponsor's protocol ID
- CDR0000413887
- Other IDs
- P30CA033572, CCC-PHI-42, NCI-6528, LAC-USC-0C-04-3, NCI-06-C-0227, NCI-P6820
- Status last verified
- Jul 2017
- First submitted
- 3 Mar 2005
- Last updated
- 19 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00104923
- Acronym / sponsor ID
- CDR0000413887
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- California Cancer ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2005
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 4 Mar 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.
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fenretinide in a different way may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating patients with refractory or relapsed hematologic cancer.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of intravenous emulsified fenretinide in patients with refractory or relapsed hematologic malignancies.
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics and in vivo activity of this drug in these patients.
- Determine, preliminarily, disease or tumor response in patients treated with this drug.
OUTLINE: This is a pilot, dose-escalation, multicenter study.
Patients receive emulsified fenretinide IV continuously over 5 days. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.
Cohorts of 1 patient receive accelerated escalating doses of fenretinide until 2 patients experience moderate toxicity (cumulative across all dose levels) OR 1 patient experiences dose-limiting toxicity (DLT). After completion of the accelerated dose-escalation portion, the standard dose-escalation portion begins. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. At least 6 patients are treated at the MTD. An additional 12 patients are treated at the MTD.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| fenretinideCurrent dose level as an IV continuous infusion via central line over 5 days. Cycle is repeated every 3 weeks for up to 6 cycles | Drug | – |
Primary outcome
To determine the maximum tolerated dose of fenretinide
Time frame: participants will be followed for the duration of cycle 1, which is expected to be 3 weeks.
To describe the toxicities of fenretinide
Time frame: participants will be followed for the duration of treatment, which is expected to be 18 weeks or less
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 19 Jul 2017.
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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.
Ann Mohrbacher, MD study chair
University of Southern California
4 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 in people with Chronic Myeloproliferative Disorders and Leukemia, run by California Cancer Consortium at 4 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?
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 19 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 determine the maximum tolerated dose of fenretinide (time frame: participants will be followed for the duration of cycle 1, which is expected to be 3 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?
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 19 Jul 2017.