Everolimus in Treating Patients With Lymphoma That Has Relapsed or Not Responded to Previous Treatment

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00436618
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 277
• Locations: 3
• Arms: 3
• Actual Duration (Months): 170.3
• Patients Per Site: 92.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying the side effects and how well everolimus works in treating patients with lymphoma that has relapsed or not responded to previous treatment.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma; Lymphoproliferative Disorder	Drug: Everolimus	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Assess the tumor response in patients with relapsed or refractory indolent non-Hodgkin lymphoma (closed to accrual as of 8/18/08), aggressive non-Hodgkin's lymphoma (closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma), or uncommon lymphoma (closed to accrual as of 9/2/08), including Hodgkin's lymphoma, treated with everolimus.

Secondary

• Evaluate overall survival, progression-free survival, and time to disease progression in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (aggressive lymphoma [closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma] vs indolent lymphoma [closed to accrual as of 8/18/08] vs uncommon lymphoma [closed to accrual as of 9/2/08]).

Patient receive oral everolimus daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue collection at baseline and periodically during study treatment for translational research studies. Blood and tissue samples are analyzed for biomarkers to study the effect of everolimus on lymphoma.

After completion of study treatment, patients are followed periodically for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 277 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Everolimus (RAD001) in Relapsed/Refractory Lymphoma
• Actual Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Oct 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relapsed aggressive non-Hodgkin lymphoma Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Drug: Everolimus; Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.; Other Names: Mayo abbreviation: RAD001
Experimental: Relapsed indolent non-Hodgkin lymphoma Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Drug: Everolimus; Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.; Other Names: Mayo abbreviation: RAD001
Experimental: Uncommon lymphomas Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Drug: Everolimus; Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.; Other Names: Mayo abbreviation: RAD001

Outcome Measures

Primary Outcome Measures

1. Tumor Response, Defined by Disease: Chronic Lymphocytic Leukemia(CLL): Clinical Complete or Complete or Nodular Partial or Partial Remission, Waldenstrom: Complete or Partial Response, All Others: Complete or Complete Unconfirmed or Partial Response. [5 years]

   CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions. Waldenstrom (subset of patients in the Uncommon Lymphomas group): >50% reduction in serum immunoglobulin M(IgM) levels (by serum protein electrophoresis (SPEP)) during any point while in this study, and no appearance of new lesions. All others: at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

Secondary Outcome Measures

1. Overall Survival [5 years]

   The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival was estimated using the method of Kaplan-Meier.

2. Progression-free Survival [5 years]

   Progression-free survival is defined as the time from registration to the time of progression or death due to any cause. Progression-free survival was estimated using the method of Kaplan-Meier. Progression is defined as the following: CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): >=50% increase in nodes from nadir or >=50% increase in liver/spleen size from nadir. Waldenstrom (subset of patients in the Uncommon Lymphomas group): >50% lymph node increase in SPD of > 1 node or new nodes, or >50% liver/spleen size increase, or > 25% IgM (by SPEP) increase, or lymphocyte morphology transformation to a more aggressive histology. All Others: New lesions or >=50% lymph nodes.

3. Time to Progression [5 years]

   The time to progression is defined as the time from registration to the time of progression. The distribution of time to progression was estimated using the method of Kaplan-Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Biopsy-proven* relapsed or refractory lymphoma, including the following:

• Aggressive lymphoma (closed to accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular lymphoma, or transformed lymphoma)

• Transformed lymphoma

• Diffuse large B-cell lymphoma

• Mantle cell lymphoma

• Grade 3 follicular lymphoma

• Precursor B-cell lymphoblastic leukemia/lymphoma

• Mediastinal (thymic) large B-cell lymphoma

• Burkitt's lymphoma/leukemia

• Precursor T-cell lymphoblastic leukemia/lymphoma

• Primary cutaneous anaplastic large cell lymphoma

• Primary systemic type anaplastic large cell lymphoma

• Indolent lymphoma (closed to accrual as of 8/18/08)

• Small lymphocytic lymphoma/chronic lymphocytic leukemia

• Grade 1 or 2 follicular lymphoma

• Extranodal marginal zone B-cell lymphoma of MALT type

• Nodal marginal zone B-cell lymphoma

• Splenic marginal zone B-cell lymphoma

• Uncommon lymphoma (closed to accrual as of 9/2/08)

• Unspecified peripheral T-cell lymphoma

• Anaplastic large cell lymphoma (T and null cell type)

• Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)

• Central Nervous System (CNS) lymphoma

• Post-transplant lymphoproliferative disorder

• Mycosis fungoides/Sezary syndrome

• Hodgkin's lymphoma

• Primary effusion lymphoma

• Blastic Natural Killer(NK)-cell lymphoma

• Adult T-cell leukemia/lymphoma

• Nasal type extranodal NK/T-cell lymphoma

• Enteropathy type T-cell lymphoma

• Hepatosplenic T-cell lymphoma

• Subcutaneous panniculitis-like T-cell lymphoma

• Angioimmunoblastic T-cell lymphoma

NOTE: *Biopsies performed < 6 months prior to study entry are allowed; biopsy-proven CNS lymphoma (at any time) does not require a re-biopsy in order to be eligible for this study

• Previously treated disease

• Patients with aggressive lymphoma (closed to accrual as of 8/24/07) OR Hodgkin's lymphoma must have received or be ineligible for potentially curative therapy, including stem cell transplantation

• Measurable disease** by CT scan or MRI, defined by 1 of the following:

• At least 1 unidimensionally measurable lesion > 2 cm in diameter

• Skin lesions may be used if they meet this criterion and are photographed with a ruler

• More than 5,000/mm³ tumor cells in the blood

NOTE: **For patients with lymphoplasmacytic lymphoma without measurable lymphadenopathy, measurable disease may be defined by bone marrow lymphoplasmacytosis with > 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy AND quantitative Immunoglobulin M(IgM) monoclonal protein > 1,000 mg/dL

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group(ECOG) performance status 0-2

• Life expectancy > 3 months

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 75,000/mm³

• Hemoglobin ≥ 8 g/dL

• Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times ULN

• aspartate aminotransferase(AST) ≤ 3 times ULN (5 times ULN if liver involvement is present)

• Creatinine ≤ 2 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Willing to provide blood samples and portion of bone marrow aspirate and biopsy during study participation

• Able to swallow intact study medication tablets

• No other life-threatening illness (unrelated to tumor)

• No serious non-malignant disease (e.g., active infection or other condition) that, in the opinion of the investigator, would preclude study participation

• No other active malignancy requiring treatment or that would preclude study participation

• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 3 weeks since prior myelosuppressive chemotherapy or biologic therapy (unless the patient has recovered from the nadir of the previous treatment)

• More than 3 weeks since prior radiotherapy (unless the acute side effects associated with therapy are resolved)

• Concurrent stable (i.e., not increased within the past month) chronic doses of corticosteroids, with a maximum dose of 20 mg of prednisone per day, is allowed if prescribed for disorders other than lymphoma (e.g., rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or asthma)

• Non-escalating doses of steroids at the lowest possible dosing level are allowed for CNS lymphoma

• No other concurrent investigational ancillary therapy

• No other concurrent chemotherapy, immunotherapy, or radiotherapy

• No concurrent participation in any other clinical trial involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Thomas E. Witzig, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00436618
• Other Study ID Numbers: MC048G; P30CA015083; MC048G; 1042-05
• First Posted: Feb 19, 2007
• Last Update Posted: Oct 22, 2019
• Last Verified: Oct 1, 2018

• Keywords provided by Mayo Clinic: recurrent adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; small intestine lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult T-cell leukemia/lymphoma; recurrent grade 3 follicular lymphoma; recurrent marginal zone lymphoma; refractory chronic lymphocytic leukemia; recurrent small lymphocytic lymphoma; recurrent mycosis fungoides/Sezary syndrome; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; recurrent adult diffuse large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent mantle cell lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; post-transplant lymphoproliferative disorder; recurrent adult diffuse small cleaved cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Leukemia; Lymphoproliferative Disorders; Everolimus

Study Results

Participant Flow

Recruitment Details	277 patients were accrued from 4 medical clinics in the United States between August 2005 and May 2010. One patient withdrew before starting treatment and thus excluded from the results.

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Period Title: Overall Study
STARTED	114	55	107
COMPLETED	84	28	46
NOT COMPLETED	30	27	61

Baseline Characteristics

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas	Total
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Total of all reporting groups
Overall Participants	114	55	107	276
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70	67	60	66
Sex: Female, Male (Count of Participants)
Female	41 36%	25 45.5%	28 26.2%	94 34.1%
Male	73 64%	30 54.5%	79 73.8%	182 65.9%
Region of Enrollment (participants) [Number]
United States	114 100%	55 100%	107 100%	276 100%
Hodgkin versus Non-Hodgkin Lymphoma (participants) [Number]
Hodgkin Lymphoma	0 0%	0 0%	29 27.1%	29 10.5%
Non-Hodgkin Lymphoma	114 100%	55 100%	78 72.9%	247 89.5%

Outcome Measures

1. Primary Outcome

Title	Tumor Response, Defined by Disease: Chronic Lymphocytic Leukemia(CLL): Clinical Complete or Complete or Nodular Partial or Partial Remission, Waldenstrom: Complete or Partial Response, All Others: Complete or Complete Unconfirmed or Partial Response.
Description	CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions. Waldenstrom (subset of patients in the Uncommon Lymphomas group): >50% reduction in serum immunoglobulin M(IgM) levels (by serum protein electrophoresis (SPEP)) during any point while in this study, and no appearance of new lesions. All others: at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

276 out of 277 were analyzed for response. One patient was excluded because of patient refusal before starting treatment.

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Measure Participants	114	55	107
Number (95% Confidence Interval) [percentage of patients in group]	26	35	49

2. Secondary Outcome

Title	Overall Survival
Description	The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival was estimated using the method of Kaplan-Meier.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

276 out of 277 were analyzed for response. One patient was excluded because of patient refusal before starting treatment.

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Measure Participants	114	55	107
Median (95% Confidence Interval) [years]	0.66	2.45	3.41

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is defined as the time from registration to the time of progression or death due to any cause. Progression-free survival was estimated using the method of Kaplan-Meier. Progression is defined as the following: CLL (subset of patients in the Relapsed Indolent Non-Hodgkin Lymphoma group): >=50% increase in nodes from nadir or >=50% increase in liver/spleen size from nadir. Waldenstrom (subset of patients in the Uncommon Lymphomas group): >50% lymph node increase in SPD of > 1 node or new nodes, or >50% liver/spleen size increase, or > 25% IgM (by SPEP) increase, or lymphocyte morphology transformation to a more aggressive histology. All Others: New lesions or >=50% lymph nodes.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

276 out of 277 were analyzed for response. One patient was excluded because of patient refusal before starting treatment.

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Measure Participants	114	55	107
Median (95% Confidence Interval) [years]	0.18	0.60	0.79

4. Secondary Outcome

Title	Time to Progression
Description	The time to progression is defined as the time from registration to the time of progression. The distribution of time to progression was estimated using the method of Kaplan-Meier.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

276 out of 277 were analyzed for response. One patient was excluded because of patient refusal before starting treatment.

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma	Relapsed Indolent Non-Hodgkin Lymphoma	Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.	Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Measure Participants	114	55	107
Median (95% Confidence Interval) [years]	0.18	0.60	0.90

Adverse Events

Arm/Group Title	Relapsed Aggressive Non-Hodgkin Lymphoma		Relapsed Indolent Non-Hodgkin Lymphoma		Uncommon Lymphomas
Arm/Group Description	Study 1. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.		Study 2. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.		Study 3. Includes Hodgkin's lymphomas. Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time. Everolimus : Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
All Cause Mortality
	Relapsed Aggressive Non-Hodgkin Lymphoma		Relapsed Indolent Non-Hodgkin Lymphoma		Uncommon Lymphomas
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Relapsed Aggressive Non-Hodgkin Lymphoma		Relapsed Indolent Non-Hodgkin Lymphoma		Uncommon Lymphomas
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/114 (33.3%)		11/55 (20%)		25/107 (23.4%)
Blood and lymphatic system disorders
Febrile neutropenia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Hemoglobin decreased	2/114 (1.8%)	2	0/55 (0%)	0	5/107 (4.7%)	6
Cardiac disorders
Atrial tachycardia	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Cardiac disorder	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Cardiopulmonary arrest	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Myocardial ischemia	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Restrictive cardiomyopathy	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Ventricular tachycardia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Colonic perforation	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Diarrhea	2/114 (1.8%)	2	0/55 (0%)	0	2/107 (1.9%)	3
Gastritis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Intra-abdominal hemorrhage	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Mucositis oral	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Nausea	3/114 (2.6%)	3	0/55 (0%)	0	0/107 (0%)	0
Upper gastrointestinal hemorrhage	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Vomiting	3/114 (2.6%)	3	0/55 (0%)	0	0/107 (0%)	0
General disorders
Disease progression	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Fatigue	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	2
Fever	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Immune system disorders
Hypersensitivity	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Infections and infestations
Biliary tract infection	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Colitis, infectious (e.g., Clostridium difficile)	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Gingival infection	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Opportunistic infection	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Pneumonia	5/114 (4.4%)	5	4/55 (7.3%)	5	4/107 (3.7%)	4
Sepsis	1/114 (0.9%)	1	2/55 (3.6%)	2	3/107 (2.8%)	3
Skin infection	1/114 (0.9%)	1	0/55 (0%)	0	2/107 (1.9%)	2
Upper respiratory infection	2/114 (1.8%)	2	0/55 (0%)	0	3/107 (2.8%)	5
Urinary tract infection	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Investigations
Creatinine increased	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Leukocyte count decreased	3/114 (2.6%)	3	0/55 (0%)	0	1/107 (0.9%)	1
Neutrophil count decreased	5/114 (4.4%)	5	3/55 (5.5%)	3	2/107 (1.9%)	2
Platelet count decreased	15/114 (13.2%)	17	5/55 (9.1%)	7	12/107 (11.2%)	18
Metabolism and nutrition disorders
Blood glucose increased	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Dehydration	3/114 (2.6%)	3	0/55 (0%)	0	0/107 (0%)	0
Serum calcium decreased	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Serum potassium decreased	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Serum sodium decreased	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Nervous system disorders
Ischemia cerebrovascular	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Speech disorder	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Psychiatric disorders
Confusion	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Depression	0/114 (0%)	0	1/55 (1.8%)	1	1/107 (0.9%)	1
Renal and urinary disorders
Renal failure	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Urethral obstruction	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Dyspnea	0/114 (0%)	0	1/55 (1.8%)	1	2/107 (1.9%)	2
Pleural effusion	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pneumonitis	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Vascular disorders
Hypertension	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Hypotension	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Thrombosis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Other (Not Including Serious) Adverse Events
	Relapsed Aggressive Non-Hodgkin Lymphoma		Relapsed Indolent Non-Hodgkin Lymphoma		Uncommon Lymphomas
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/114 (99.1%)		55/55 (100%)		107/107 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	0/114 (0%)	0	0/55 (0%)	0	3/107 (2.8%)	4
Hemoglobin decreased	107/114 (93.9%)	426	49/55 (89.1%)	207	103/107 (96.3%)	770
Cardiac disorders
Atrial fibrillation	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Cardiac disorder	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Cardiac pain	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Left ventricular failure	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	3
Myocardial ischemia	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	2
Myocarditis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Palpitations	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Restrictive cardiomyopathy	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Supraventricular tachycardia	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Ventricular tachycardia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Ear and labyrinth disorders
Hearing impaired	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	2
Endocrine disorders
Adrenal insufficiency	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Eye disorders
Eye disorder	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	2
Gastrointestinal disorders
Abdominal distension	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Abdominal pain	2/114 (1.8%)	2	2/55 (3.6%)	2	2/107 (1.9%)	2
Constipation	2/114 (1.8%)	4	1/55 (1.8%)	5	2/107 (1.9%)	2
Diarrhea	37/114 (32.5%)	57	22/55 (40%)	48	41/107 (38.3%)	93
Dry mouth	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	3
Dyspepsia	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Dysphagia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Ear, nose and throat examination abnormal	1/114 (0.9%)	1	1/55 (1.8%)	2	1/107 (0.9%)	1
Gastrointestinal disorder	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Hemorrhoids	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Mucositis oral	13/114 (11.4%)	16	8/55 (14.5%)	11	21/107 (19.6%)	27
Nausea	33/114 (28.9%)	46	17/55 (30.9%)	22	35/107 (32.7%)	54
Oral pain	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pancreatitis	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Proctoscopy abnormal	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Rectal hemorrhage	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Rectal pain	1/114 (0.9%)	1	0/55 (0%)	0	2/107 (1.9%)	2
Vomiting	26/114 (22.8%)	31	7/55 (12.7%)	8	21/107 (19.6%)	29
General disorders
Chills	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Disease progression	1/114 (0.9%)	1	1/55 (1.8%)	1	0/107 (0%)	0
Edema limbs	4/114 (3.5%)	7	1/55 (1.8%)	8	4/107 (3.7%)	18
Fatigue	34/114 (29.8%)	42	21/55 (38.2%)	22	32/107 (29.9%)	63
Fever	8/114 (7%)	8	2/55 (3.6%)	2	1/107 (0.9%)	1
General symptom	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Ill-defined disorder	1/114 (0.9%)	2	0/55 (0%)	0	0/107 (0%)	0
Pain	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Visceral edema	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Hepatobiliary disorders
Gallbladder obstruction	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Infections and infestations
Abdominal infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Anal infection	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Bladder infection	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Bronchitis	0/114 (0%)	0	2/55 (3.6%)	3	2/107 (1.9%)	2
Catheter related infection	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Cecal infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Colitis, infectious (e.g., Clostridium difficile)	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Gastric infection	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	2
Gingival infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Infection	2/114 (1.8%)	2	1/55 (1.8%)	1	3/107 (2.8%)	3
Lip infection	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Mucosal infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Otitis externa	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	2
Penile infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Pharyngitis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pleural infection	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pneumonia	5/114 (4.4%)	6	6/55 (10.9%)	6	9/107 (8.4%)	11
Sepsis	0/114 (0%)	0	2/55 (3.6%)	2	2/107 (1.9%)	3
Sinusitis	2/114 (1.8%)	3	2/55 (3.6%)	2	4/107 (3.7%)	5
Skin infection	7/114 (6.1%)	8	2/55 (3.6%)	2	4/107 (3.7%)	5
Tooth infection	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Upper aerodigestive tract infection	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Upper respiratory infection	2/114 (1.8%)	2	1/55 (1.8%)	1	7/107 (6.5%)	10
Urinary tract infection	3/114 (2.6%)	3	1/55 (1.8%)	2	2/107 (1.9%)	4
Viral hepatitis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Wound infection	0/114 (0%)	0	1/55 (1.8%)	2	1/107 (0.9%)	2
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Vascular access complication	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	2
Investigations
Alanine aminotransferase increased	0/114 (0%)	0	0/55 (0%)	0	2/107 (1.9%)	5
Alkaline phosphatase increased	1/114 (0.9%)	1	0/55 (0%)	0	5/107 (4.7%)	12
Aspartate aminotransferase increased	8/114 (7%)	12	3/55 (5.5%)	3	2/107 (1.9%)	7
Cardiac troponin I increased	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Creatinine increased	3/114 (2.6%)	3	0/55 (0%)	0	5/107 (4.7%)	5
Leukocyte count decreased	70/114 (61.4%)	190	25/55 (45.5%)	78	67/107 (62.6%)	285
Lymphocyte count decreased	0/114 (0%)	0	1/55 (1.8%)	2	0/107 (0%)	0
Neutrophil count decreased	62/114 (54.4%)	106	25/55 (45.5%)	58	51/107 (47.7%)	148
Platelet count decreased	91/114 (79.8%)	380	40/55 (72.7%)	177	74/107 (69.2%)	375
Serum cholesterol increased	12/114 (10.5%)	21	6/55 (10.9%)	13	7/107 (6.5%)	16
Weight loss	4/114 (3.5%)	4	1/55 (1.8%)	2	5/107 (4.7%)	14
Metabolism and nutrition disorders
Anorexia	9/114 (7.9%)	10	3/55 (5.5%)	3	4/107 (3.7%)	5
Blood glucose increased	27/114 (23.7%)	45	8/55 (14.5%)	19	15/107 (14%)	31
Blood uric acid increased	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Dehydration	1/114 (0.9%)	1	2/55 (3.6%)	2	1/107 (0.9%)	1
Glucose intolerance	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Serum albumin decreased	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Serum calcium decreased	0/114 (0%)	0	0/55 (0%)	0	3/107 (2.8%)	3
Serum glucose decreased	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Serum potassium decreased	0/114 (0%)	0	1/55 (1.8%)	1	2/107 (1.9%)	2
Serum potassium increased	2/114 (1.8%)	3	0/55 (0%)	0	1/107 (0.9%)	1
Serum sodium decreased	1/114 (0.9%)	1	3/55 (5.5%)	3	1/107 (0.9%)	1
Serum triglycerides increased	14/114 (12.3%)	24	7/55 (12.7%)	13	9/107 (8.4%)	25
Tumor lysis syndrome	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	5/114 (4.4%)	6	3/55 (5.5%)	4	5/107 (4.7%)	7
Arthritis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Back pain	2/114 (1.8%)	2	0/55 (0%)	0	3/107 (2.8%)	3
Chest wall pain	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Muscle weakness	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Myalgia	3/114 (2.6%)	3	3/55 (5.5%)	4	6/107 (5.6%)	6
Osteoporosis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Pain in extremity	0/114 (0%)	0	1/55 (1.8%)	1	1/107 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Nervous system disorders
Accessory nerve disorder	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Ataxia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Dizziness	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Dysgeusia	4/114 (3.5%)	6	1/55 (1.8%)	1	4/107 (3.7%)	6
Headache	3/114 (2.6%)	3	0/55 (0%)	0	3/107 (2.8%)	3
Ischemia cerebrovascular	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Mini mental status examination abnormal	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Neurological disorder NOS	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	2
Peripheral motor neuropathy	3/114 (2.6%)	4	0/55 (0%)	0	0/107 (0%)	0
Peripheral sensory neuropathy	4/114 (3.5%)	25	0/55 (0%)	0	4/107 (3.7%)	4
Radiculitis brachial	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Speech disorder	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Tremor	1/114 (0.9%)	1	0/55 (0%)	0	1/107 (0.9%)	1
Trigeminal nerve disorder	1/114 (0.9%)	3	0/55 (0%)	0	0/107 (0%)	0
Psychiatric disorders
Confusion	1/114 (0.9%)	1	1/55 (1.8%)	1	0/107 (0%)	0
Depression	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Insomnia	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Renal and urinary disorders
Renal failure	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Ureteric stenosis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Urinary incontinence	0/114 (0%)	0	1/55 (1.8%)	1	1/107 (0.9%)	1
Urinary retention	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Cough	4/114 (3.5%)	4	4/55 (7.3%)	5	4/107 (3.7%)	4
Dyspnea	9/114 (7.9%)	10	2/55 (3.6%)	4	9/107 (8.4%)	11
Epistaxis	1/114 (0.9%)	1	2/55 (3.6%)	2	3/107 (2.8%)	3
Hiccups	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Hypoxia	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Laryngeal mucositis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Laryngoscopy abnormal	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pharyngeal examination abnormal	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Pharyngeal stenosis	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Pleural effusion	0/114 (0%)	0	0/55 (0%)	0	3/107 (2.8%)	3
Pleuritic pain	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Pneumonitis	4/114 (3.5%)	6	4/55 (7.3%)	4	4/107 (3.7%)	4
Pulmonary fibrosis	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Pulmonary hemorrhage	0/114 (0%)	0	1/55 (1.8%)	1	0/107 (0%)	0
Voice alteration	1/114 (0.9%)	1	0/55 (0%)	0	0/107 (0%)	0
Skin and subcutaneous tissue disorders
Dry skin	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1
Nail disorder	1/114 (0.9%)	1	0/55 (0%)	0	2/107 (1.9%)	2
Pruritus	0/114 (0%)	0	0/55 (0%)	0	4/107 (3.7%)	8
Rash acneiform	2/114 (1.8%)	2	1/55 (1.8%)	1	1/107 (0.9%)	3
Rash desquamating	8/114 (7%)	11	5/55 (9.1%)	6	13/107 (12.1%)	15
Skin disorder	0/114 (0%)	0	1/55 (1.8%)	2	1/107 (0.9%)	1
Sweating	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	6
Vascular disorders
Hypertension	0/114 (0%)	0	1/55 (1.8%)	3	0/107 (0%)	0
Hypotension	0/114 (0%)	0	1/55 (1.8%)	1	2/107 (1.9%)	2
Thrombosis	2/114 (1.8%)	2	0/55 (0%)	0	0/107 (0%)	0
Vascular disorder	0/114 (0%)	0	0/55 (0%)	0	1/107 (0.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.