CTCLPhase 1NCT04171791
A Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL)
A Phase 1 study testing ABT-199 (venetoclax) in people with CTCL, run by Yale University at 1 site in United States.
Trial summary
The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CTCL
- What is being tested?
- ABT-199 (venetoclax)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2020to 22 Jun 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides), stage IB-IV (hereafter referred to as advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable.
- All subjects must have shown disease refractory to one or more standard systemic therapy (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or total skin electron beam therapy over 3 months, or have demonstrated relapsed or progressive disease at any time while receiving one or more of therapies.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Adequate bone marrow function: WBC > 2000/µL; platelet count > 75,000/mm3; Neutrophil count > 1000/µL, without use of colony stimulating factors (CSF).
- Required washout period for prior therapies
- Spot Skin Radiation Therapy (≤10% skin surface): 4 weeks
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- Systemic therapy: 4 weeks, or until recovered from toxicities
- Women of child-bearing potential must have negative serum pregnancy test and use accepted highly effective methods of birth control throughout the study and for 90 days after dosing and must agree to use effective contraception, such as hormonal birth control (must be at least 3 years without complications), intrauterine devices, double barrier method (condom plus spermicide or diaphragm), or abstain from sexual intercourse.
- Male patients must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study and for 90 days after dosing.
- Adequate hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), AST ≤3.0 x ULN, ALT ≤ 3.0 x ULN
- Adequate renal function: creatinine clearance ≥ 50 mL/min
- Ability to comply with the treatment schedule
Who cannot join
- Extracutaneous disease except blood, bone marrow and lymph nodes.
- Concomitant use of any systemic anti-cancer therapy or immune modifier.
- Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of study drug administration.
- Patients receiving P-gp inhibitors are not eligible for inclusion unless these agents are discontinued for a washout period of 4 weeks. Patients who are taking medications that are narrow window index P-gp substrates (e.g. digoxin, fexofenadine, loperamide, quinidine, talinolol, vinblastine) are not eligible for enrollment.
- Patients with biopsy confirmed transformed MF.
- Prior allogeneic hematopoietic cell transplant.
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- Any ongoing infection requiring antibiotics within 2 weeks prior to the start of the study drug, except for antibiotics (e.g. cephalexin) prescribed superficial skin infection.
- Known history of human immunodeficiency virus (HIV), hepatitis B or C.
- History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA <1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years.
- Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study including, but not limited to, the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions.
- Major surgery within 8 weeks of enrollment.
- Medically significant cardiac event or unstable cardiovascular function defined as:
- Symptomatic ischemia, unstable angina pectoris
- Uncontrolled clinically significant cardiac arrhythmia
- Symptomatic heart failure NYHA Class ≥ 3
- Myocardial infarction or cardiac surgery within 6 months prior to enrollment
- Cerebrovascular event (transient ischemic attack, stroke or CNS bleeding) within the last 12 months.
- Major bleeding within the last 6 months.
- Use of any investigational agents within 30 days prior to enrollment and for the duration of the study.
- Pregnant or lactating.
- Unwilling or unable to provide informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital / Smilow Cancer Center
New Haven, Connecticut, 06520
About this study
Official title: A Single Arm, Open-Label Pilot Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL) Stage IB to IV
The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.
Read the detailed description
This is a single arm, open-label, non-randomized study with venetoclax (ABT-199) in CTCL patients (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides). This study is planned to be conducted in 18 patients, 18 years or older in age, undergoing a 5-week dose escalation protocol (per the US FDA package insert guidelines of venetoclax for CLL). Safety monitoring will continue throughout the whole period of drug administration and the treatment will be discontinued if intolerable toxicity (defined in Stopping Rules) or disease progression occurs during this period.
- Conditions
- CTCL
- Being tested
- ABT-199 (venetoclax)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-199 (venetoclax)Drug
Eligible patients will be enrolled into the study and receive venetoclax daily per the US FDA package insert guidelines of venetoclax, with dose escalation up to 400 mg. To minimize the risk of tumor lysis syndrome (TLS), and following the package insert directions for dose escalation over 5 weeks, the initial dose is 20 mg daily, and may be progressively increased as tolerated to 400 mg by week 5.
| Study group | Role | What they receive |
|---|---|---|
| ABT-199 (Venetoclax) | Experimental | Patients with Cutaneous T Cell Lymphoma (CTCL) will receive ABT-199 (Venetoclax). Receives: Drug: ABT-199 (venetoclax) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body Temperature
Safety and tolerability endpoints will be evaluated on the basis of body temperature.
Measured: Up to 32 weeks
Blood Pressure- Diastolic
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
Measured: Up to 32 weeks
Blood Pressure- Systolic
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
Measured: Up to 32 weeks
Pulse Rate
Safety and tolerability endpoints will be evaluated on the basis of pulse rate.
Measured: Up to 32 weeks
Respiratory Rate
Safety and tolerability endpoints will be evaluated on the basis of respiratory rate.
Measured: Up to 32 weeks
Adverse Events
Adverse events will be used to measure the study defined outcome:Toxicity. Toxicity (as adverse events) will measured according to the NCI CTCAE (v5.0) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of venetoclax and up to four weeks after last dose (Termination visit).
Measured: Up to 32 weeks
Secondary outcomes (3)
Skin Clinical Response
Exploratory skin clinical responses measured by a modified severity-weighted assessment tool (mSWAT).
Measured: Up to 32 weeks
Duration of Response
Duration of response to treatment will be measured in weeks.
Measured: Up to 32 weeks
Relapse Free and Progression Free Survival
Relapse free and progression free survival based on every 4 week follow up after the initial dose until one of the events occurs first: Progressive disease (PD) is documented, another anticancer treatment is administered and/or 28 weeks are completed after the patient's first dose of venetoclax.
Measured: Up to 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start15 Jan 2020
- Primary completion10 Feb 2021
- Study completion22 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CTCLStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Girardi, MD, FAAD, Principal investigator, Professor of Dermatology Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04171791
- Sponsor's protocol ID
- 2000022803
- Status last verified
- Jun 2021
- First submitted
- 29 Oct 2019
- Last updated
- 25 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open-Label Pilot Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL) Stage IB to IV
- ClinicalTrials.gov ID
- NCT04171791
- Acronym / sponsor ID
- 2000022803
- Conditions
- CTCL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 10 Feb 2021 (actual)
- Study completion
- 22 Jun 2021 (actual)
- First posted
- 21 Nov 2019 (actual)
- 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 objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.
Detailed description
This is a single arm, open-label, non-randomized study with venetoclax (ABT-199) in CTCL patients (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides). This study is planned to be conducted in 18 patients, 18 years or older in age, undergoing a 5-week dose escalation protocol (per the US FDA package insert guidelines of venetoclax for CLL). Safety monitoring will continue throughout the whole period of drug administration and the treatment will be discontinued if intolerable toxicity (defined in Stopping Rules) or disease progression occurs during this period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ABT-199 (Venetoclax) | Experimental | Drug: ABT-199 (venetoclax)Patients with Cutaneous T Cell Lymphoma (CTCL) will receive ABT-199 (Venetoclax). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides), stage IB-IV (hereafter referred to as advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable.
- All subjects must have shown disease refractory to one or more standard systemic therapy (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or total skin electron beam therapy over 3 months, or have demonstrated relapsed or progressive disease at any time while receiving one or more of therapies.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Adequate bone marrow function: WBC > 2000/µL; platelet count > 75,000/mm3; Neutrophil count > 1000/µL, without use of colony stimulating factors (CSF).
- Required washout period for prior therapies
Key exclusion criteria (21 listed)
- Extracutaneous disease except blood, bone marrow and lymph nodes.
- Concomitant use of any systemic anti-cancer therapy or immune modifier.
- Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of study drug administration.
- Patients receiving P-gp inhibitors are not eligible for inclusion unless these agents are discontinued for a washout period of 4 weeks. Patients who are taking medications that are narrow window index P-gp substrates (e.g. digoxin, fexofenadine, loperamide, quinidine, talinolol, vinblastine) are not eligible for enrollment.
- Patients with biopsy confirmed transformed MF.
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 |
|---|---|---|
| ABT-199 (venetoclax)Eligible patients will be enrolled into the study and receive venetoclax daily per the US FDA package insert guidelines of venetoclax, with dose escalation up to 400 mg. To minimize the risk of tumor lysis syndrome (TLS), and following the package insert directions for dose escalation over 5 weeks, the initial dose is 20 mg daily, and may be progressively increased as tolerated to 400 mg by week 5. | Drug | ABT-199 (Venetoclax) |
Primary outcome
Body Temperature
Time frame: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of body temperature.
Blood Pressure- Diastolic
Time frame: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
Blood Pressure- Systolic
Time frame: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
Pulse Rate
Time frame: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of pulse rate.
Respiratory Rate
Time frame: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of respiratory rate.
Adverse Events
Time frame: Up to 32 weeks
Adverse events will be used to measure the study defined outcome:Toxicity. Toxicity (as adverse events) will measured according to the NCI CTCAE (v5.0) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of venetoclax and up to four weeks after last dose (Termination visit).
3 secondary outcomes
Skin Clinical Response
Time frame: Up to 32 weeks
Duration of Response
Time frame: Up to 32 weeks
Relapse Free and Progression Free Survival
Time frame: Up to 32 weeks
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 25 Jun 2021.
- Individual participant dataSharing planned: No
Related trials for CTCL
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
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Not yet recruitingPhase 2
Golidocitinib in Patients With Mycosis Fungoides/Sézary Syndrome and T-Cell Large Granular Lymphocytic Leukemia
Mycosis Fungoides/Sezary Syndrome, T-cell Large Granular Lymphocytic Leukemia
RecruitingObservational study
Tissue Repository: CTCL Collection Protocol
Lymphoma, T-Cell, Cutaneous, Lymphomatoid Papulosis
RecruitingObservational study
Characterization of the Microbiome in Cutaneous T Cell Lymphoma
Cutaneous T Cell Lymphoma
RecruitingObservational study
Collection of Human Samples to Study Hairy Cell and Other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment
Hairy Cell Leukemia (HCL), Chronic Lymphocytic Leukemia (CLL)
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.
Michael Girardi, MD, FAAD principal investigator
Professor of Dermatology Yale University
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 ABT-199 (venetoclax) in people with CTCL, run by Yale University 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 12 inclusion and 21 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 25 Jun 2021. 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?
Body Temperature (time frame: Up to 32 weeks). The study lists 6 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 25 Jun 2021.