Mycosis FungoidesPhase 1NCT01445340
Topical Romidepsin to Treat Early-Stage Cutaneous T-Cell Lymphoma
A Phase 1 study testing Romidepsin (FR901228) in people with Mycosis Fungoides and Cutaneous T-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Cutaneous T-cell lymphoma (CTCL) is a rare, slow-growing form of skin cancer. The cancer cells are found in red, scaly patches that may sometimes itch. Early-stage CTCL is usually treated with topical therapies, which may lose effectiveness over time and have adverse effects, such as risk of secondary skin… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Mycosis Fungoides, Cutaneous T-Cell Lymphoma, Neoplasms
- What is being tested?
- Romidepsin (FR901228)
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2007to 29 Jun 2012
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a pathologically confirmed diagnosis of CTCL based on a skin biopsy, utilizing standard histological criteria based on cytological, architectural, and immunophenotypic findings. In cases with equivocal histological features, the diagnosis may be verified or confirmed through the use of clonal T-cell gamma gene rearrangement, as detected by PCR amplification and primer sets specific for the T-cell receptor gamma chain genes.
- Patients must have early stage CTCL (Stage IA, IB, or IIA as defined by TNM staging system).
- Patients must:
- be age greater than or equal to 18 years.
- have evaluable disease.
- have a performance status of ECOG 0-1.
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- be either on no therapy or only on topical therapy for early stage CTCL. Patients must have stopped light therapy (i.e. PUVA, UVB) for at least 2 weeks prior to the use of study medication. Patients must have stopped topical therapies (i.e. corticosteroids or nitrogen mustard) to designated target sites or areas to be treated with study medication for at least 2 weeks prior to the use of study medication. (Topical therapies for CTCL may be continued to non-adjacent, non-target lesions while on protocol.) Patients may have received other HDACI therapy but must have stopped systemic therapy 4 weeks prior to use of study medication.
- be able to give written informed consent.
- be willing to return to the National Cancer Institute for follow-up.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. The effects of romidepsin on the developing human fetus are unknown. For this reason and because HDAC Inhibitor agents are known to be teratogenic, patients that are pregnant or lactating will be excluded from this trial.
- Laboratory values:
- Within 7 days prior to registration: absolute neutrophil count greater than or equal to 1000/microL, platelets greater than or equal to 100,000/microL, bilirubin (total and direct) less than or equal to 1.5 times upper limit of normal, and AST less than or equal to 3 times upper limit of normal, creatinine less than or equal to 1.5 times upper limit of normal, or documented creatinine clearance of greater than or equal to 60mL/min
- Cardiac findings:
- Within 4 weeks of registration: ECG [patients should not have QTc prolongation (greater than 480 msec) and/or rhythm abnormality; allowance of other EKG changes will be at discretion of the investigator based on consultation with a cardiologist] and echocardiogram [demonstrating normal ejection fraction].
- Subjects from both genders and all racial/ethnic groups are eligible for this study if they meet the eligibility criteria.
Who cannot join
- Prior or concurrent malignancies that have not been curatively treated with the exception of malignancies that have been curatively treated and without recurrence in the preceding 5 years, non-melanoma skin cancers, low grade cervical cancer and prostate cancer.
- Current or previous CNS metastasis.
- Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C, and 8 weeks for UCN-01.
- HIV seropositivity.
- Pregnant or breast-feeding patients.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Use of known CYP3A4 inhibitors within 3 days prior to receiving romidepsin ointment treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase I Study of Topical Romidepsin (Depsipeptide) in Early Stage Cutaneous T-Cell Lymphoma
Background:
- Cutaneous T-cell lymphoma (CTCL) is a rare, slow-growing form of skin cancer. The cancer cells are found in red, scaly patches that may sometimes itch.
- Early-stage CTCL is usually treated with topical therapies, which may lose effectiveness over time and have adverse effects, such as risk of secondary skin cancers and difficulty of use.
- Romidepsin is an experimental drug that, given through a vein, has improved CTCL in some patients with later stages of the disease.
- A topical ointment form of romidepsin may be helpful in treating early-stage CTCL.
Read more
Objectives:
- To determine the highest tolerated dose of topical romidepsin that can be given to patients with early-stage CTCL.
- To evaluate the effectiveness of topical romidepsin in patients with early-stage CTCL.
- To determine how the body handles topical romidepsin.
Eligibility:
-Patients 18 of age and older with early-stage CTCL.
Design:
- Study Part 1: Successive groups of 3 patients are treated with increasingly higher concentrations of topical romidepsin until the highest tolerated dose is found.
- Study Part II: The highest tolerated dose, as determined in Part I, is applied to larger areas of skin in another group of patients.
- All study participants apply the study medicine to their skin three times a day for 4 weeks.
- During treatment, participants are monitored at weeks 2 and 4 with a history and physical examination, blood tests, electrocardiogram, skin biopsies and photographs of the skin.
- After stopping treatment, participants return to the clinic at weeks 6 and 8 for blood tests and to see how the study medication is affecting the body.
Read the detailed description
Background:
- Romidepsin is a histone deacetylase inhibitor which has demonstrated efficacy and tolerability as an infusion in later stages of cutaneous T-cell lymphoma (CTCL).
- Early stages of CTCL are typically treated with skin-directed therapies, which may lose efficacy over time and have adverse effects (i.e. risk of secondary skin cancers, difficulty of use).
- A topical form of romidepsin may be helpful in the treatment of early-stage CTCL.
Objectives:
- Primary - To define the maximal tolerated dose (MTD) of topical romidepsin for early-stage CTCL when administered three times weekly, then escalated first in concentration, followed by increased frequency and lastly over increasing body surface areas.
- Secondary - To assess histone acetylation in topical romidepsin-treated skin.
- Secondary - To assess in a pilot fashion clinical efficacy of topical romidepsin in early stage cutaneous T-cell lymphoma.
- Secondary - To perform pharmacokinetic monitoring of blood levels of romidepsin in topically treated patients.
Eligibility:
-Patients age greater than or equal to 18 with confirmed early-stage (stage IA, IB, or IIA) cutaneous T-cell lymphoma.
Design:
- A Cohorts of Three design to define the MTD of topical romidepsin in Aquaphor ointment initially applied overnight, three times weekly for 4 weeks, then escalated first in concentration, followed by increased frequency and lastly over increasing body surface areas.
- Skin toxicities, systemic toxicities, and disease response will be assessed throughout the study.
- The primary focus of the first part of the protocol will be to evaluate local skin toxicity, beginning with dose level 1 of 0.05 percent topical romidepsin on 25 cm(2) target area (0.005 mg/ cm(2). If tolerated, progress to higher dose levels of 0.25 percent (0.025 mg/ cm(2); dose level 2) and then 0.5 percent (0.05 mg/ cm(2); dose level 3) topical romidepsin on 25 cm(2) target area. Systemic toxicity will also be monitored.
- To date, we have completed the first 4 dose levels and have not yet established cutaneous MTD. To achieve this, we will proceed to the second part of the protocol, which will increase the concentration to 1%, then increase the frequency to daily application, then progress to 2% concentration, then 4% concentration, and then applying to progressively larger body surface areas. Our aim is to more fully address systemic toxicity by increasing drug concentration, application frequency, and body surface area (BSA) treated. We will utilize topical romidepsin at the MTD on increasing BSA (lesional \& nonlesional skin): multiple lesions up to 3% BSA (dose level 4), multiple lesions up to 25% BSA (dose level 7A), 50% BSA (dose level 7B), and 75% or > BSA (dose level 7C).
- Conditions
- Mycosis Fungoides, Cutaneous T-Cell Lymphoma, Neoplasms
- Being tested
- Romidepsin (FR901228)
- Keywords
- Topical Depsi, Cutaneous T Cell Lymphoma, CTCL, Mycosis Fungoides
- Medical subject headings
- Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Romidepsin (FR901228)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To define the maximal tolerated dose of topical romidepsin.
Secondary outcomes (1)
To assess histone acetylation in topical romidepsin-treated skin, to assess in a pilot fashion clinical efficacy of topical romidepsin in early stage CTCL and to perform pharmacokinetic monitoring of blood levels of topical romidepsin.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study start21 Apr 2007
- Study completion29 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mycosis FungoidesStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Heidi H Kong, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445340
- Sponsor's protocol ID
- 070133
- Other IDs
- 07-C-0133
- Status last verified
- 29 Jun 2012
- First submitted
- 30 Sep 2011
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Ueda H, Nakajima H, Hori Y, Goto T, Okuhara M. Action of FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum no. 968, on Ha-ras transformed NIH3T3 cells. Biosci Biotechnol Biochem. 1994 Sep;58(9):1579-83. doi: 10.1271/bbb.58.1579.
PubMed 7765477Kitazono M, Chuman Y, Aikou T, Fojo T. Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab. 2001 Feb;86(2):834-40. doi: 10.1210/jcem.86.2.7196.
PubMed 11158054Ueda H, Manda T, Matsumoto S, Mukumoto S, Nishigaki F, Kawamura I, Shimomura K. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. J Antibiot (Tokyo). 1994 Mar;47(3):315-23. doi: 10.7164/antibiotics.47.315.
PubMed 8175484
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Topical Romidepsin (Depsipeptide) in Early Stage Cutaneous T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01445340
- Acronym / sponsor ID
- 070133
- Conditions
- Mycosis Fungoides, Cutaneous T-Cell Lymphoma, Neoplasms
- Keywords
- Topical Depsi, Cutaneous T Cell Lymphoma, CTCL, Mycosis Fungoides
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 21 Apr 2007
- Study completion
- 29 Jun 2012 (actual)
- First posted
- 3 Oct 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.
Background:
- Cutaneous T-cell lymphoma (CTCL) is a rare, slow-growing form of skin cancer. The cancer cells are found in red, scaly patches that may sometimes itch.
- Early-stage CTCL is usually treated with topical therapies, which may lose effectiveness over time and have adverse effects, such as risk of secondary skin cancers and difficulty of use.
- Romidepsin is an experimental drug that, given through a vein, has improved CTCL in some patients with later stages of the disease.
- A topical ointment form of romidepsin may be helpful in treating early-stage CTCL.
Objectives:
- To determine the highest tolerated dose of topical romidepsin that can be given to patients with early-stage CTCL.
- To evaluate the effectiveness of topical romidepsin in patients with early-stage CTCL.
- To determine how the body handles topical romidepsin.
Eligibility:
-Patients 18 of age and older with early-stage CTCL.
Design:
- Study Part 1: Successive groups of 3 patients are treated with increasingly higher concentrations of topical romidepsin until the highest tolerated dose is found.
- Study Part II: The highest tolerated dose, as determined in Part I, is applied to larger areas of skin in another group of patients.
- All study participants apply the study medicine to their skin three times a day for 4 weeks.
- During treatment, participants are monitored at weeks 2 and 4 with a history and physical examination, blood tests, electrocardiogram, skin biopsies and photographs of the skin.
- After stopping treatment, participants return to the clinic at weeks 6 and 8 for blood tests and to see how the study medication is affecting the body.
Detailed description
Background:
- Romidepsin is a histone deacetylase inhibitor which has demonstrated efficacy and tolerability as an infusion in later stages of cutaneous T-cell lymphoma (CTCL).
- Early stages of CTCL are typically treated with skin-directed therapies, which may lose efficacy over time and have adverse effects (i.e. risk of secondary skin cancers, difficulty of use).
- A topical form of romidepsin may be helpful in the treatment of early-stage CTCL.
Objectives:
- Primary - To define the maximal tolerated dose (MTD) of topical romidepsin for early-stage CTCL when administered three times weekly, then escalated first in concentration, followed by increased frequency and lastly over increasing body surface areas.
- Secondary - To assess histone acetylation in topical romidepsin-treated skin.
- Secondary - To assess in a pilot fashion clinical efficacy of topical romidepsin in early stage cutaneous T-cell lymphoma.
- Secondary - To perform pharmacokinetic monitoring of blood levels of romidepsin in topically treated patients.
Eligibility:
-Patients age greater than or equal to 18 with confirmed early-stage (stage IA, IB, or IIA) cutaneous T-cell lymphoma.
Design:
- A Cohorts of Three design to define the MTD of topical romidepsin in Aquaphor ointment initially applied overnight, three times weekly for 4 weeks, then escalated first in concentration, followed by increased frequency and lastly over increasing body surface areas.
- Skin toxicities, systemic toxicities, and disease response will be assessed throughout the study.
- The primary focus of the first part of the protocol will be to evaluate local skin toxicity, beginning with dose level 1 of 0.05 percent topical romidepsin on 25 cm(2) target area (0.005 mg/ cm(2). If tolerated, progress to higher dose levels of 0.25 percent (0.025 mg/ cm(2); dose level 2) and then 0.5 percent (0.05 mg/ cm(2); dose level 3) topical romidepsin on 25 cm(2) target area. Systemic toxicity will also be monitored.
- To date, we have completed the first 4 dose levels and have not yet established cutaneous MTD. To achieve this, we will proceed to the second part of the protocol, which will increase the concentration to 1%, then increase the frequency to daily application, then progress to 2% concentration, then 4% concentration, and then applying to progressively larger body surface areas. Our aim is to more fully address systemic toxicity by increasing drug concentration, application frequency, and body surface area (BSA) treated. We will utilize topical romidepsin at the MTD on increasing BSA (lesional \& nonlesional skin): multiple lesions up to 3% BSA (dose level 4), multiple lesions up to 25% BSA (dose level 7A), 50% BSA (dose level 7B), and 75% or > BSA (dose level 7C).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Within 7 days prior to registration: absolute neutrophil count greater than or equal to 1000/microL, platelets greater than or equal to 100,000/microL, bilirubin (total and direct) less than or equal to 1.5 times upper limit of normal, and AST less than or equal to 3 times upper limit of normal, creatinine less than or equal to 1.5 times upper limit of normal, or documented creatinine clearance of greater than or equal to 60mL/min
- Within 4 weeks of registration: ECG [patients should not have QTc prolongation (greater than 480 msec) and/or rhythm abnormality; allowance of other EKG changes will be at discretion of the investigator based on consultation with a cardiologist] and echocardiogram [demonstrating normal ejection fraction].
- Subjects from both genders and all racial/ethnic groups are eligible for this study if they meet the eligibility criteria.
Key exclusion criteria (7 listed)
- Prior or concurrent malignancies that have not been curatively treated with the exception of malignancies that have been curatively treated and without recurrence in the preceding 5 years, non-melanoma skin cancers, low grade cervical cancer and prostate cancer.
- Current or previous CNS metastasis.
- Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C, and 8 weeks for UCN-01.
- HIV seropositivity.
- Pregnant or breast-feeding patients.
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 |
|---|---|---|
| Romidepsin (FR901228) | Drug | – |
Primary outcome
To define the maximal tolerated dose of topical romidepsin.
1 secondary outcome
To assess histone acetylation in topical romidepsin-treated skin, to assess in a pilot fashion clinical efficacy of topical romidepsin in early stage CTCL and to perform pharmacokinetic monitoring of blood levels of topical romidepsin.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 7765477Ueda H, Nakajima H, Hori Y, Goto T, Okuhara M. Action of FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum no. 968, on Ha-ras transformed NIH3T3 cells. Biosci Biotechnol Biochem. 1994 Sep;58(9):1579-83. doi: 10.1271/bbb.58.1579.
- Background: PubMed 11158054Kitazono M, Chuman Y, Aikou T, Fojo T. Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab. 2001 Feb;86(2):834-40. doi: 10.1210/jcem.86.2.7196.
- Background: PubMed 8175484Ueda H, Manda T, Matsumoto S, Mukumoto S, Nishigaki F, Kawamura I, Shimomura K. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. J Antibiot (Tokyo). 1994 Mar;47(3):315-23. doi: 10.7164/antibiotics.47.315.
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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.
Heidi H Kong, M.D. principal investigator
National Cancer Institute (NCI)
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 Romidepsin (FR901228) in people with Mycosis Fungoides and Cutaneous T-Cell Lymphoma, 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 15 inclusion and 7 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 17 Dec 2019. 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 was stopped early. 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?
To define the maximal tolerated dose of topical romidepsin.. 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 NCT01445340, which also lists 3 linked publications.
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 Dec 2019.