## Protocol Section
### Identification Module
**NCT ID:** NCT01687179

**Acronym:** SAIL

**Brief Title:** Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis

**Official Title:** Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus

#### Organization Study ID Info
**ID:** SAIL-1100
#### Organization
**Class:** OTHER
**Full Name:** Brigham and Women's Hospital
#### Secondary ID Infos
**ID:** 1ZIAHL002541-21
**Link:** https://reporter.nih.gov/quickSearch/1ZIAHL002541-21
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2015-08

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-10-11

**Type:** ACTUAL

**Last Update Submit Date:** 2018-09-13

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2015-08

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2018-10-11

**Type:** ACTUAL

**Results First Submit Date:** 2017-03-30

**Results First Submit QC Date:** 2018-09-13

#### Start Date
**Date:** 2012-09

**Status Verified Date:** 2018-09

#### Study First Post Date
**Date:** 2012-09-18
**Type:** ESTIMATED
**Study First Submit Date:** 2012-08-02
**Study First Submit QC Date:** 2012-09-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Heart, Lung, and Blood Institute (NHLBI)

#### Lead Sponsor

**Class:** OTHER

**Name:** Brigham and Women's Hospital

#### Responsible Party

**Investigator Affiliation:** Brigham and Women's Hospital

**Investigator Full Name:** Elizabeth Henske

**Investigator Title:** Overall Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief 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 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.

### Conditions Module

**Conditions:**

- Lymphangioleiomyomatosis

**Keywords:**

- LAM

- TSC

- lymphangioleiomyomatosis

### Design Module

#### Design Info

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 14

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: "Sirolimus" and "Hydroxychloroquine" 200 mg

- Drug: "Sirolimus" and "Hydroxychloroquine" 400 mg

**Label:** "Sirolimus" and "Hydroxychloroquine"

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- "Sirolimus" and "Hydroxychloroquine"

**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 taken orally daily.

**Name:** "Sirolimus" and "Hydroxychloroquine" 200 mg

**Other Names:**

- sirolimus(rapamune), hydroxychloroquine (plaquenil)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- "Sirolimus" and "Hydroxychloroquine"

**Description:** 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.

**Name:** "Sirolimus" and "Hydroxychloroquine" 400 mg

**Other Names:**

- Sirolimus (Rapamune), Hydroxychloroquine (plaquenil)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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".

**Measure:** Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients

**Time Frame:** 48 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* 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

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Boston

**Country:** United States

**Facility:** Brigham and Women's Hospital

**State:** Massachusetts

**Zip:** 02120

#### Overall Officials

**Official 1:**

**Affiliation:** Brigham and Women's Hospital

**Name:** Elizabeth P Henske, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** National Heart, Lung, and Blood Institute (NHLBI)

**Name:** Joel Moss, MD, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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.

**PMID:** 31299246

**Citation:** Lamattina 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.

**PMID:** 30144422

**Citation:** El-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.

**PMID:** 28192114

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000008203

- Term: Lymphangiomyoma

- ID: D000018190

- Term: Lymphatic Vessel Tumors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000054973

- Term: Perivascular Epithelioid Cell Neoplasms

- ID: D000018204

- Term: Neoplasms, Connective and Soft Tissue

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M20338

- Name: Lymphangioleiomyomatosis

- Relevance: HIGH

- As Found: Lymphangioleiomyomatosis

- ID: M11200

- Name: Lymphangiomyoma

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M27983

- Name: Perivascular Epithelioid Cell Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M20350

- Name: Neoplasms, Connective and Soft Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3526

- Name: Lymphangioleiomyomatosis

- Relevance: HIGH

- As Found: Lymphangioleiomyomatosis

### Condition Browse Module - Meshes

- ID: D000018192

- Term: Lymphangioleiomyomatosis

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000000903

- Term: Antibiotics, Antineoplastic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000935

- Term: Antifungal Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000962

- Term: Antimalarials

- ID: D000000981

- Term: Antiprotozoal Agents

- ID: D000000977

- Term: Antiparasitic Agents

- ID: D000018501

- Term: Antirheumatic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

### Intervention Browse Module - Browse Leaves

- ID: M21960

- Name: Sirolimus

- Relevance: HIGH

- As Found: Included

- ID: M9940

- Name: Hydroxychloroquine

- Relevance: HIGH

- As Found: Bone marrow

- ID: M353695

- Name: Temsirolimus

- Relevance: HIGH

- As Found: Included

- ID: M2827

- Name: MTOR Inhibitors

- Relevance: HIGH

- As Found: Included

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M6252

- Name: Clotrimazole

- Relevance: LOW

- As Found: Unknown

- ID: M11796

- Name: Miconazole

- Relevance: LOW

- As Found: Unknown

- ID: M4254

- Name: Antifungal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M4280

- Name: Antimalarials

- Relevance: LOW

- As Found: Unknown

- ID: M4298

- Name: Antiprotozoal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4294

- Name: Antiparasitic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000020123

- Term: Sirolimus

- ID: D000006886

- Term: Hydroxychloroquine

- ID: C000401859

- Term: Temsirolimus

- ID: D000091203

- Term: MTOR Inhibitors

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Sirolimus and Hydroxychloroquine 200 mg

**Deaths Num At Risk:** 3

**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 taken orally daily.

**ID:** EG000

**Other Num Affected:** 3

**Other Num at Risk:** 3

**Serious Number At Risk:** 3

**Title:** Sirolimus and Hydroxychloroquine 200 mg

**Group ID:** EG001

**Title:** Sirolimus and Hydroxychloroquine 400 mg

**Deaths Num At Risk:** 10

**Description:** 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.

**ID:** EG001

**Other Num Affected:** 9

**Other Num at Risk:** 10

**Serious Number Affected:** 1

**Serious Number At Risk:** 10

**Title:** Sirolimus and Hydroxychloroquine 400 mg

**Frequency Threshold:** 0

#### Other Events

**Term:** Rash/ Acne

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Skin and subcutaneous tissue disorders

**Source Vocabulary:** CTCAE (4.0)

**Term:** Abnormal Investigations

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** CTCAE (4.0)

**Term:** Diarrhea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** CTCAE (4.0)

**Term:** Oral Mucositis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** CTCAE (4.0)

#### Serious Events

**Term:** radiculitis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** CTCAE (4.0)

##### Stats

**Group ID:** EG000

**Num At Risk:** 3

**Group ID:** EG001

**Num Affected:** 1

**Num At Risk:** 10

**Num Events:** 1

**Time Frame:** 48 weeks

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 14

**Units:** Participants

### Group

**ID:** BG000

**Title:** Sirolimus and Hydroxychloroquine

**Description:** 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 or twice a day for 6 months, depending on time of enrollment into the study, following a standard phase I dose escalation.

sirolimus and hydroxychloroquine: 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.

### Measure

#### Measurement

**Group ID:** BG000

**Lower Limit:** 40

**Upper Limit:** 65

**Value:** 49

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 13

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Male

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 12

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Unknown or Not Reported

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 13

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** United States

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 6

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 9

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 2

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 14

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 8

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 103

**Value:** 442

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 19.2

**Value:** 43.8

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 0.33

**Value:** 3.11

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 0.7

**Value:** 1.6

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 21

**Value:** 59

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 14

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 0.7

**Value:** 2.8

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 16

**Value:** 81

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 3.1

**Value:** 9.8

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 15

**Value:** 43

#### Denomination

**Units:** Participants

##### Denomination Counts

**Group ID:** BG000

**Value:** 13

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** FULL_RANGE
**Parameter Type:** MEDIAN
**Population Description:** 1 subject screen failed.
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Region of Enrollment
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Post-Menopause
**Unit of Measure:** Participants
### Measure 6
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Pneumothorax
**Unit of Measure:** Participants
### Measure 7
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Angiomyolipoma
**Unit of Measure:** Participants
### Measure 8
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Tuberous Sclerois (TSC)- Lymphangioleiomyomatosis (LAM)
**Unit of Measure:** Participants
### Measure 9
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed.
**Title:** Lung Biopsy
**Unit of Measure:** Participants
### Measure 10
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Population Description:** 1 subject screen failed
**Title:** Chylothorax
**Unit of Measure:** Participants
### Measure 11
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 subject screen failed.
**Title:** 6 minute walk distance (6MWD) (m)
**Unit of Measure:** m
### Measure 12
**Description:** The Saint George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 subject screen failed.
**Title:** St. George's Respiratory Questionnaire (SGRQ)
**Unit of Measure:** units on a scale
### Measure 13
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 subject screen failed.
**Title:** Log VEGF-D (Veascular Endothelial Growth factor)
**Unit of Measure:** log(pg/ml)
### Measure 14
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 Subject Screen failed.
**Title:** FEV1
**Unit of Measure:** Litres
### Measure 15
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** FEV1 (%)
**Unit of Measure:** Percent predicted
### Measure 16
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 subject screen failed.
**Title:** FVC (L)
**Unit of Measure:** Litres
### Measure 17
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 Subject Screen failed.
**Title:** FVC (%)
**Unit of Measure:** Percent predicted
### Measure 18
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 Subject screen failed.
**Title:** DLCO (ml/min/mmhg)
**Unit of Measure:** ml/min/mmhg
### Measure 19
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Population Description:** 1 Subject screen failed.
**Title:** DLCO (%)
**Unit of Measure:** percent predicted
**Population Description:** 1 subject failed to qualify for the study at the screening visit. Since the subject had signed consent, we considered the participant to be enrolled on the study.
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** ehenske@bwh.harvard.edu
**Organization:** Brigham and Women's Hospital
**Phone:** 857-307-0782
**Title:** Elizabeth P. Henske, MD
## Results Section - Outcome Measures Module
### Outcome Measure 1
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2.27
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1.11
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1.11
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 18.18
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 22.22
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 18.18
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6.67
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0.56
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 15.91
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 8.33
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0.56
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6.82
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 20
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3.33
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 4.44
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 4.55
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5.00
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0.56
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 7.78
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6.82
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1.11
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2.27
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 9.44
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 25.0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6.11
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1.67
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** 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".
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** 48 weeks
**Title:** Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
**Type:** PRIMARY
**Unit of Measure:** Percentage of adverse events
##### Group
**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 taken orally daily. Safety of the drug combination was assessed by the occurrence of adverse events in these 3 patients.
**ID:** OG000
**Title:** Sirolimus and Hydroxychloroquine 200 mg
##### Group
**Description:** 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. Safety of this dose was assessed by the occurrence of adverse events in these 10 patients.
**ID:** OG001
**Title:** Sirolimus and Hydroxychloroquine 400 mg
### Participant Flow Module
#### Group
**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 taken orally daily.
**ID:** FG000
**Title:** Sirolimus and Hydroxychloroquine 200 mg
#### Group
**Description:** 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.
**ID:** FG001
**Title:** Sirolimus and HydroxyChloroquine 400 mg
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 3
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 10
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 2
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 6
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 1
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 4
**Has Results:** True