CCI-779 and Rituximab in Treating Patients With Relapsed... | NCT00109967

ID	Type	Description	Link
N038H
U10CA025224	U.S. NIH Grant/Contract		View source
CDR0000425334	Registry Identifier	PDQ (Physician Data Query)

Description Module

Label	Type	Description	Intervention Names
Arm I	Experimental	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.	Biological: rituximab Drug: temsirolimus

Name	Type	Description	Arm Group Labels	Other Names
rituximab	Biological	375 mg/m^2 Given IV	Arm I	IDEC-C2B8

Measure	Description	Time Frame
Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria	Complete Response (CR) - Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms. Partial Response (PR) requires a >=50% decrease in sum of the products of the greatest dimension (SPD) of the six largest dominant nodes or nodal masses. Overall Response Rate (ORR) - The number of patients who achieve a CR or PR divided by the total number of evaluable patients. We report the Overall Response Rate here.	Up to 12, 28-day cycles.

Measure	Description	Time Frame
Time to Progression	Time to progression was defined as the time from registration to the date of progression. Patients who died without disease progression were censored at the date of their last evaluation. Patients who were still receiving treatment at the time of these analyses were censored at the date of their last evaluation. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed* mantle cell lymphoma (MCL)
- Relapsed, refractory, or stable disease after prior treatment
- Tumor must be cyclin D-1 by immunohistochemistry OR 11;14 translocation by fluorescent in situ hybridization or cytogenetics
Measurable disease, defined as ≥ 1 of the following:
- Unidimensionally measurable lymph node or tumor mass ≥ 2 cm by CT scan or MRI
- Splenic enlargement if spleen is palpable ≥ 3 cm below the left costal margin
- Malignant lymphocytosis if absolute lymphocytic count ≥ 5,000 AND lymphocytes confirmed to be monoclonal by flow cytometry
No known central nervous system involvement (e.g., parenchymal mass or leptomeningeal involvement)
Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
At least 3 months
No other concurrent treatment for MCL
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Direct bilirubin < 1.5 times ULN
Aspartate aminotransferase (AST) ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)
Creatinine ≤ 2 times ULN
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Cholesterol ≤ 350 mg/dL
Fasting triglycerides < 400 mg/dL
No known HIV positivity
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness
No other active malignancy requiring treatment OR that would preclude assessment of response to study drugs
Prior biologic response modifiers allowed
Prior immunotherapy allowed
Prior high-dose therapy with stem cell support (i.e., stem cell transplantation) allowed
No concurrent prophylactic growth factor to support neutrophils
Prior chemotherapy allowed
No other concurrent chemotherapy
No concurrent corticosteroids to induce an antitumor response
- Concurrent corticosteroids (≤ 10 mg/day of prednisone or equivalent) for adrenal insufficiency or acute allergic reactions allowed
Prior radiotherapy allowed
No prior treatment with a mammalian target of rapamycin (mTOR) inhibitor
No other concurrent investigational or commercial agents or therapies for MCL
No other concurrent immunosuppressive therapy

Name	Affiliation	Role
Stephen Ansell	North Central Cancer Treatment Group	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mobile Infirmary Medical Center		Mobile	Alabama	36607	United States
The Medical Center of Aurora

PubMed Identifier	Type	Citation	Retractions
21440503	Derived	Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, Erlichman C, Witzig TE. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol. 2011 Apr;12(4):361-8. doi: 10.1016/S1470-2045(11)70062-6.

ID	Title	Description
FG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria

Complete Response (CR) - Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.

Partial Response (PR) requires a >=50% decrease in sum of the products of the greatest dimension (SPD) of the six largest dominant nodes or nodal masses.

Overall Response Rate (ORR) - The number of patients who achieve a CR or PR divided by the total number of evaluable patients.

We report the Overall Response Rate here.

Posted

Number

95% Confidence Interval

percentage of patients

Up to 12, 28-day cycles.

ID	Title	Description
OG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
OG001	Group II: Rituximab Refractory	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Units	Counts
Participants	OG00048 OG00121

Title

Denominators

Categories

Title	Measurements
	OG00062.5(47.4 to 76.1) OG00152.4(29.8 to 74.3)

Secondary

Time to Progression

Time to progression was defined as the time from registration to the date of progression. Patients who died without disease progression were censored at the date of their last evaluation. Patients who were still receiving treatment at the time of these analyses were censored at the date of their last evaluation. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.

Posted

Median

95% Confidence Interval

months

Patients were followed up to five years after registration.

ID	Title	Description
OG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
OG001	Group II: Rituximab Refractory	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Secondary

Duration of Response

Duration of response was defined as the time from the date of documented response to the date of progression. Patients who went off treatment due to other reasons (eg, adverse reactions, refusal of further treatment) were censored at that time. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.

Of the 48 Rituximab Sensitive patients, 30 patients had a response. Of the 21 Rituximab Refractory patients, 11 patients had a response. Therefore, this endpoint uses 30 patients from the Rituximab Sensitive group and 11 patients from the Rituximab Refractory group in the analysis.

Posted

Median

95% Confidence Interval

months

Response duration is followed up to 5 years from registration.

ID	Title	Description
OG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Secondary

Toxicity

As per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3, toxicity was defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment by the treating physician.

In this section, we report the number of participants that experienced at least one Grade 3 or higher adverse event.

Posted

Number

patients

Assessed during treatment (up to 12, 28-day cycles)

ID	Title	Description
OG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
OG001	Group II: Rituximab Refractory	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Secondary

Overall Survival

Overall survival (OS) was defined as the time from registration to death resulting from any cause. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.

Posted

Median

95% Confidence Interval

months

Patients were followed for survival status for up to 5 years.

ID	Title	Description
OG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
OG001	Group II: Rituximab Refractory	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hemoglobin decreased	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Left ventricular failure	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Myocardial ischemia	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Rectal pain	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Death NOS	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Disease progression	General disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Fever	General disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Localized edema	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Hypersensitivity	Immune system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Catheter related infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0010 events0 affected21 at risk
Pneumonia	Infections and infestations	MedDRA 6	Systematic Assessment	EG0004 events4 affected48 at risk EG0011 events1 affected21 at risk
Skin infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Soft tissue infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Leukocyte count decreased	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Neutrophil count decreased	Investigations	MedDRA 6	Systematic Assessment	EG0005 events3 affected48 at risk EG0011 events1 affected21 at risk
Platelet count decreased	Investigations	MedDRA 6	Systematic Assessment	EG0005 events3 affected48 at risk EG0012 events2 affected21 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Serum calcium decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Encephalopathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Tremor	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Renal failure	Renal and urinary disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events2 affected21 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0011 events1 affected21 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0005 events4 affected48 at risk EG0011 events1 affected21 at risk
Hematoma	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hemorrhage	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Thrombosis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hemoglobin decreased	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG000143 events29 affected48 at risk EG00188 events16 affected21 at risk
Hemolysis	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events1 affected21 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0010 events0 affected21 at risk
Pericardial effusion	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
External ear pain	Ear and labyrinth disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Endocrine disorder	Endocrine disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hypothyroidism	Endocrine disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Dry eye syndrome	Eye disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0019 events1 affected21 at risk
Eye disorder	Eye disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Eye pain	Eye disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Photophobia	Eye disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0010 events0 affected21 at risk
Watering eyes	Eye disorders	MedDRA 6	Systematic Assessment	EG0004 events1 affected48 at risk EG0013 events1 affected21 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Anal exam abnormal	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Constipation	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG00021 events6 affected48 at risk EG0019 events4 affected21 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG00051 events16 affected48 at risk EG00110 events6 affected21 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0003 events2 affected48 at risk EG0015 events1 affected21 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0006 events3 affected48 at risk EG0010 events0 affected21 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Ear, nose and throat examination abnormal	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0014 events3 affected21 at risk
Esophageal mucositis	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Esophagitis	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Flatulence	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Gastric mucositis	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Gastroscopy abnormal	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Gingival pain	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG00047 events19 affected48 at risk EG0015 events5 affected21 at risk
Nausea	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG00020 events11 affected48 at risk EG00125 events10 affected21 at risk
Oral pain	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0012 events1 affected21 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Vomiting	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0004 events3 affected48 at risk EG0012 events1 affected21 at risk
Chest pain	General disorders	MedDRA 6	Systematic Assessment	EG0004 events2 affected48 at risk EG0010 events0 affected21 at risk
Chills	General disorders	MedDRA 6	Systematic Assessment	EG0003 events2 affected48 at risk EG0011 events1 affected21 at risk
Disease progression	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Edema limbs	General disorders	MedDRA 6	Systematic Assessment	EG00050 events14 affected48 at risk EG00118 events5 affected21 at risk
Fatigue	General disorders	MedDRA 6	Systematic Assessment	EG000170 events36 affected48 at risk EG00174 events16 affected21 at risk
Fever	General disorders	MedDRA 6	Systematic Assessment	EG0005 events4 affected48 at risk EG0011 events1 affected21 at risk
Localized edema	General disorders	MedDRA 6	Systematic Assessment	EG0008 events1 affected48 at risk EG0010 events0 affected21 at risk
Pain	General disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected48 at risk EG0010 events0 affected21 at risk
Hypersensitivity	Immune system disorders	MedDRA 6	Systematic Assessment	EG0004 events3 affected48 at risk EG0011 events1 affected21 at risk
Bladder infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Bronchitis	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0011 events1 affected21 at risk
Eye infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0011 events1 affected21 at risk
Gingival infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0011 events1 affected21 at risk
Infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0003 events3 affected48 at risk EG0011 events1 affected21 at risk
Nail infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0010 events0 affected21 at risk
Pneumonia	Infections and infestations	MedDRA 6	Systematic Assessment	EG0003 events3 affected48 at risk EG0013 events2 affected21 at risk
Sinusitis	Infections and infestations	MedDRA 6	Systematic Assessment	EG0004 events2 affected48 at risk EG0012 events2 affected21 at risk
Skin infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events2 affected21 at risk
Small intestine infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Upper respiratory infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0012 events2 affected21 at risk
Urinary tract infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Bruising	Injury, poisoning and procedural complications	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Alanine aminotransferase increased	Investigations	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0014 events2 affected21 at risk
Alkaline phosphatase increased	Investigations	MedDRA 6	Systematic Assessment	EG00025 events7 affected48 at risk EG0017 events6 affected21 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 6	Systematic Assessment	EG0008 events4 affected48 at risk EG0017 events4 affected21 at risk
Creatinine increased	Investigations	MedDRA 6	Systematic Assessment	EG00030 events6 affected48 at risk EG00116 events5 affected21 at risk
INR increased	Investigations	MedDRA 6	Systematic Assessment	EG00019 events5 affected48 at risk EG0010 events0 affected21 at risk
Laboratory test abnormal	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events1 affected21 at risk
Leukocyte count decreased	Investigations	MedDRA 6	Systematic Assessment	EG000174 events28 affected48 at risk EG00168 events16 affected21 at risk
Lipase increased	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Lymphocyte count decreased	Investigations	MedDRA 6	Systematic Assessment	EG00064 events7 affected48 at risk EG00120 events3 affected21 at risk
Neutrophil count decreased	Investigations	MedDRA 6	Systematic Assessment	EG00097 events21 affected48 at risk EG00138 events13 affected21 at risk
Platelet count decreased	Investigations	MedDRA 6	Systematic Assessment	EG000176 events34 affected48 at risk EG00175 events15 affected21 at risk
Serum cholesterol increased	Investigations	MedDRA 6	Systematic Assessment	EG000136 events35 affected48 at risk EG00145 events15 affected21 at risk
Weight loss	Investigations	MedDRA 6	Systematic Assessment	EG00027 events13 affected48 at risk EG00126 events7 affected21 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG00027 events13 affected48 at risk EG00122 events9 affected21 at risk
Blood bicarbonate decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Blood glucose increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG00045 events21 affected48 at risk EG00138 events11 affected21 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0010 events0 affected21 at risk
Serum albumin decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG00012 events6 affected48 at risk EG0012 events2 affected21 at risk
Serum calcium decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG00028 events8 affected48 at risk EG0012 events2 affected21 at risk
Serum calcium increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events2 affected21 at risk
Serum glucose decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0007 events2 affected48 at risk EG0010 events0 affected21 at risk
Serum magnesium decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Serum phosphate decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Serum potassium decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0006 events4 affected48 at risk EG0017 events4 affected21 at risk
Serum potassium increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0011 events1 affected21 at risk
Serum sodium decreased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0009 events5 affected48 at risk EG0015 events2 affected21 at risk
Serum sodium increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0016 events1 affected21 at risk
Serum triglycerides increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG000151 events37 affected48 at risk EG00163 events16 affected21 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG00019 events7 affected48 at risk EG0011 events1 affected21 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG00014 events5 affected48 at risk EG0011 events1 affected21 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0006 events2 affected48 at risk EG0013 events3 affected21 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0011 events1 affected21 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0008 events5 affected48 at risk EG0012 events1 affected21 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0010 events0 affected21 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0004 events4 affected48 at risk EG0011 events1 affected21 at risk
Dizziness	Nervous system disorders	MedDRA 6	Systematic Assessment	EG00015 events5 affected48 at risk EG0012 events2 affected21 at risk
Dysgeusia	Nervous system disorders	MedDRA 6	Systematic Assessment	EG00030 events12 affected48 at risk EG0016 events2 affected21 at risk
Headache	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0008 events6 affected48 at risk EG0012 events2 affected21 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0006 events4 affected48 at risk EG0012 events2 affected21 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG00041 events12 affected48 at risk EG00117 events5 affected21 at risk
Syncope	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Tremor	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Anxiety	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG00010 events3 affected48 at risk EG0010 events0 affected21 at risk
Confusion	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0006 events1 affected48 at risk EG0011 events1 affected21 at risk
Depression	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0007 events2 affected48 at risk EG0010 events0 affected21 at risk
Insomnia	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0007 events4 affected48 at risk EG0013 events2 affected21 at risk
Urinary frequency	Renal and urinary disorders	MedDRA 6	Systematic Assessment	EG0009 events2 affected48 at risk EG0010 events0 affected21 at risk
Reproductive tract disorder	Reproductive system and breast disorders	MedDRA 6	Systematic Assessment	EG0004 events1 affected48 at risk EG0010 events0 affected21 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0007 events3 affected48 at risk EG0013 events3 affected21 at risk
Apnea	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG00013 events9 affected48 at risk EG00112 events3 affected21 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG00014 events8 affected48 at risk EG0019 events5 affected21 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG00014 events4 affected48 at risk EG0016 events2 affected21 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Laryngoscopy abnormal	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0003 events1 affected48 at risk EG0014 events3 affected21 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG00015 events9 affected48 at risk EG0011 events1 affected21 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events1 affected21 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0007 events4 affected48 at risk EG0011 events1 affected21 at risk
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0004 events2 affected48 at risk EG0010 events0 affected21 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG00112 events1 affected21 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG00112 events1 affected21 at risk
Hand-and-foot syndrome	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG00031 events10 affected48 at risk EG00113 events3 affected21 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0012 events1 affected21 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG00015 events6 affected48 at risk EG00110 events3 affected21 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0005 events3 affected48 at risk EG0011 events1 affected21 at risk
Rash desquamating	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG00088 events26 affected48 at risk EG00140 events12 affected21 at risk
Skin atrophy	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected48 at risk EG0010 events0 affected21 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0007 events1 affected48 at risk EG0010 events0 affected21 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0009 events1 affected48 at risk EG0010 events0 affected21 at risk
Sweating	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0004 events2 affected48 at risk EG0010 events0 affected21 at risk
Flushing	Vascular disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected48 at risk EG0011 events1 affected21 at risk
Hemorrhage	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hot flashes	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Hypertension	Vascular disorders	MedDRA 6	Systematic Assessment	EG0006 events2 affected48 at risk EG0010 events0 affected21 at risk
Hypotension	Vascular disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected48 at risk EG0010 events0 affected21 at risk
Phlebitis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected48 at risk EG0010 events0 affected21 at risk
Thrombosis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected48 at risk EG0012 events1 affected21 at risk

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals

ID	Title	Description
BG000	Group I: Rituximab Sensitive	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
BG001	Group II: Rituximab Refractory	Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment. rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group I: Rituximab Sensitive	temsirolimus: 25 mg given IV			16	48	48	48
EG001	Group II: Rituximab Refractory	temsirolimus: 25 mg given IV			7	21	21	21