LymphangioleiomyomatosisPhase 1SAILNCT01687179
Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis
A Phase 1 study testing "Sirolimus" and "Hydroxychloroquine" 200 mg and "Sirolimus" and "Hydroxychloroquine" 400 mg in people with Lymphangioleiomyomatosis, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of… Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Lymphangioleiomyomatosis
- What is being tested?
- "Sirolimus" and "Hydroxychloroquine" 200 mg and "Sirolimus" and "Hydroxychloroquine" 400 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Aug 2015
- Phase
- Phase 1
- 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 18 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female age 18 or older
- Ability to give informed consent
- Diagnosis of LAM as defined as typical cystic change on CT plus:
- biopsy or cytology of any tissue demonstrating LAM
- angiomyolipoma, chylothorax, lymphangioleiomyoma, or tuberous sclerosis
- serum VEGFD greater or equal to 800pg/ml
- Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or less than 70% of predicted, or RV > 120% of predicted at baseline
- Women of childbearing potential must agree to use 2 forms of barrier contraception during and for 8 weeks after the last dose of medication.
Who cannot join
- History of intolerance of mTOR inhibitors
- History of intolerance to hydroxychloroquine
- History of severe psoriasis
- History of porphyria cutanea tarda
- Uncontrolled intercurrent illness
- Pregnant, breast feeding, or plan to become pregnant in the next year
Show all 28Show fewer
- Inadequate contraception
- Significant hematological or hepatic abnormalities
- Use of an investigational drug within 30 days of study start
- Inability to attend scheduled clinic visits
- Inability to perform PFTs
- Creatinine > 2.5mg/dL
- Recent pneumothorax within 8 weeks of screening
- History of malignancy in the last 2 years other than basal cell skin cancer
- Use of estrogen containing medication within 30 days of screening
- Abnormal G6PD levels at baseline
- Preexisting maculopathy or retinopathy
- Preexisting myopathy
- Currently taking doxycycline, metformin, lupron, simvastatin
- Unable to undergo CT or MRI
- History of seizure within last year
- Hepatitis B, C, HIV positive serology
- Use of alternative medical therapies for LAM for at least 6 weeks prior to study participation
- History of myocardial infarct, angina, or stroke related to atherosclerosis
- History of cardiomyopathy
- Previous lung transplant
- Surgery (involving entry into a body cavity or requiring 3 or more stitches) within 2 months of initiation of study drug
- Uncontrolled cholesterol > 350mg/dL, triglycerides > 400mg/dL
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
Official title: Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus
Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated
Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy.
Read more
Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy.
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. Up to 18 adult women with LAM will be enrolled.
Read the detailed description
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The protocol will use the following eligibility criteria.
- Conditions
- Lymphangioleiomyomatosis
- Being tested
- "Sirolimus" and "Hydroxychloroquine" 200 mg, "Sirolimus" and "Hydroxychloroquine" 400 mg
- Keywords
- LAM, TSC, lymphangioleiomyomatosis
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Sirolimus" and "Hydroxychloroquine" 200 mgDrug
Also called sirolimus(rapamune), hydroxychloroquine (plaquenil)
This will be a phase I dose escalation study of the combination of "Sirolimus" (2 mg adjusted to keep trough levels between 5-15 ng/ml) and "Hydroxychloroquine" 200 mg taken orally daily.
"Sirolimus" and "Hydroxychloroquine" 400 mgDrug
Also called Sirolimus (Rapamune), Hydroxychloroquine (plaquenil)
Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day.
| Study group | Role | What they receive |
|---|---|---|
| "Sirolimus" and "Hydroxychloroquine" | Experimental | Subjects will take Sirolimus at an initial dose of 2mg followed by dose adjustment to keep Sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to Sirolimus subjects will receive Hydroxychloroquine at 200 mg daily for 6 months. Once safety is established at the lower dose ("Sirolimus" and "Hydroxychloroquine" 200 mg), subjects enrolled henceforth will receive Sirolimus and Hydroxychloroquine 400 mg (200 mg twice a day) for 6 months. Receives: Drug: "Sirolimus" and "Hydroxychloroquine" 200 mg; Drug: "Sirolimus" and "Hydroxychloroquine" 400 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0".
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionAug 2015
- Study completionAug 2015
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphangioleiomyomatosisStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Elizabeth Henske, Brigham and Women's Hospital
- Investigators
- Elizabeth P Henske, MD, Principal investigator, Brigham and Women's HospitalJoel Moss, MD, PhD, Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687179
- Sponsor's protocol ID
- SAIL-1100
- Other IDs
- 1ZIAHL002541-21
- Acronym
- SAIL
- Status last verified
- Sep 2018
- First submitted
- 2 Aug 2012
- Last updated
- 11 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Tang Y, El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Rosas IO, Moss J, Priolo C, Henske EP. Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells. Chest. 2019 Dec;156(6):1137-1148. doi: 10.1016/j.chest.2019.05.038. Epub 2019 Jul 9.
PubMed 31299246Lamattina AM, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Cui Y, Rosas IO, Moss J, Henske EP, El-Chemaly S. Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018 Nov;154(5):1070-1082. doi: 10.1016/j.chest.2018.08.1029. Epub 2018 Aug 23.
PubMed 30144422El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Peters E, Haughey M, Bienfang D, Jones AM, Julien-Williams P, Cui Y, Villalba JA, Bagwe S, Maurer R, Rosas IO, Moss J, Henske EP. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017 Jun;151(6):1302-1310. doi: 10.1016/j.chest.2017.01.033. Epub 2017 Feb 10.
PubMed 28192114
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus
- ClinicalTrials.gov ID
- NCT01687179
- Acronym / sponsor ID
- SAIL / SAIL-1100
- Conditions
- Lymphangioleiomyomatosis
- Keywords
- LAM, TSC, lymphangioleiomyomatosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 18 Sep 2012 (estimated)
- Results
- Posted 11 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated
Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy.
Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy.
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. Up to 18 adult women with LAM will be enrolled.
Detailed description
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The protocol will use the following eligibility criteria.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| "Sirolimus" and "Hydroxychloroquine" | Experimental | Drug: "Sirolimus" and "Hydroxychloroquine" 200 mg, Drug: "Sirolimus" and "Hydroxychloroquine" 400 mgSubjects will take Sirolimus at an initial dose of 2mg followed by dose adjustment to keep Sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to Sirolimus subjects will receive Hydroxychloroquine at 200 mg daily for 6 months. Once safety is established at the lower dose ("Sirolimus" and "Hydroxychloroquine" 200 mg), subjects enrolled henceforth will receive Sirolimus and Hydroxychloroquine 400 mg (200 mg twice a day) for 6 months. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female age 18 or older
- Ability to give informed consent
- Diagnosis of LAM as defined as typical cystic change on CT plus:
- Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or less than 70% of predicted, or RV > 120% of predicted at baseline
- Women of childbearing potential must agree to use 2 forms of barrier contraception during and for 8 weeks after the last dose of medication.
Key exclusion criteria (28 listed)
- History of intolerance of mTOR inhibitors
- History of intolerance to hydroxychloroquine
- History of severe psoriasis
- History of porphyria cutanea tarda
- Uncontrolled intercurrent illness
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 |
|---|---|---|
| "Sirolimus" and "Hydroxychloroquine" 200 mgAlso: sirolimus(rapamune), hydroxychloroquine (plaquenil)This will be a phase I dose escalation study of the combination of "Sirolimus" (2 mg adjusted to keep trough levels between 5-15 ng/ml) and "Hydroxychloroquine" 200 mg taken orally daily. | Drug | "Sirolimus" and "Hydroxychloroquine" |
| "Sirolimus" and "Hydroxychloroquine" 400 mgAlso: Sirolimus (Rapamune), Hydroxychloroquine (plaquenil)Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. | Drug | "Sirolimus" and "Hydroxychloroquine" |
Primary outcome
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Time frame: 48 weeks
The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0".
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31299246Tang Y, El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Rosas IO, Moss J, Priolo C, Henske EP. Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells. Chest. 2019 Dec;156(6):1137-1148. doi: 10.1016/j.chest.2019.05.038. Epub 2019 Jul 9.
- Derived from this study: PubMed 30144422Lamattina AM, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Cui Y, Rosas IO, Moss J, Henske EP, El-Chemaly S. Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018 Nov;154(5):1070-1082. doi: 10.1016/j.chest.2018.08.1029. Epub 2018 Aug 23.
- Derived from this study: PubMed 28192114El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Peters E, Haughey M, Bienfang D, Jones AM, Julien-Williams P, Cui Y, Villalba JA, Bagwe S, Maurer R, Rosas IO, Moss J, Henske EP. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017 Jun;151(6):1302-1310. doi: 10.1016/j.chest.2017.01.033. Epub 2017 Feb 10.
- Individual participant dataSharing planned: No
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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.
Elizabeth P Henske, MD principal investigator
Brigham and Women's Hospital
Joel Moss, MD, PhD principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 "Sirolimus" and "Hydroxychloroquine" 200 mg and "Sirolimus" and "Hydroxychloroquine" 400 mg in people with Lymphangioleiomyomatosis, run by Brigham and Women's Hospital 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 8 inclusion and 28 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 11 Oct 2018. 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?
Yes. Results are posted in the registry (first posted 11 Oct 2018). 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?
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients (time frame: 48 weeks). 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 NCT01687179, 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 11 Oct 2018.