CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00109967
• Collaborator: (none)
• Enrollment: 71
• Locations: 195
• Arm: 1
• Duration (Months): 82
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving CCI-779 together with rituximab works in treating patients with relapsed or refractory mantle cell lymphoma. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving CCI-779 together with rituximab may kill more cancer cells

Condition or Disease	Intervention/Treatment	Phase
Recurrent Mantle Cell Lymphoma	Biological: rituximab; Drug: temsirolimus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.

2. Determine the tolerability of this regimen in these patients by assessing toxicity.

SECONDARY OBJECTIVES:

1. Determine the time to disease progression and overall survival of patients treated with this regimen.

2. Determine the duration of response in patients treated with this regimen.

OUTLINE: Patients are stratified according to prior response to rituximab (sensitive [partial response (PR) or complete response (CR) that lasted ≥ 6 months after the last treatment with rituximab alone or in combination with chemotherapy] vs refractory [stable or progressive disease OR a PR or CR that lasted < 6 months after the last treatment with rituximab alone or in combination with chemotherapy]).

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.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm I 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; 375 mg/m^2 Given IV; Other Names: IDEC-C2B8 IDEC-C2B8 monoclonal antibody Mabthera MOAB IDEC-C2B8 Rituxan ; Drug: temsirolimus; 25 mg given IV; Other Names: CCI-779 cell cycle inhibitor 779 Torisel

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria [Up to 12, 28-day cycles.]

   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.

Secondary Outcome Measures

1. Time to Progression [Patients were followed up to five years after registration.]

   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.

2. Duration of Response [Response duration is followed up to 5 years from registration.]

   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.

3. Toxicity [Assessed during treatment (up to 12, 28-day cycles)]

   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.

4. Overall Survival [Patients were followed for survival status for up to 5 years.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36607
2	The Medical Center of Aurora	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301
4	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
5	Saint Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
8	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
15	Longmont United Hospital	Longmont	Colorado	United States	80501
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
18	North Suburban Medical Center	Thornton	Colorado	United States	80229
19	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
20	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
21	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
22	Graham Hospital Association	Canton	Illinois	United States	61520
23	Memorial Hospital	Carthage	Illinois	United States	62321
24	Eureka Hospital	Eureka	Illinois	United States	61530
25	Galesburg Clinic	Galesburg	Illinois	United States	61401
26	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
27	Mason District Hospital	Havana	Illinois	United States	62644
28	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
29	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
30	Kewanee Hospital	Kewanee	Illinois	United States	61443
31	Mcdonough District Hospital	Macomb	Illinois	United States	61455
32	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
33	Community Cancer Center Foundation	Normal	Illinois	United States	61761
34	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
35	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
36	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
37	Pekin Hospital	Pekin	Illinois	United States	61554
38	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
39	Proctor Hospital	Peoria	Illinois	United States	61614
40	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
41	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
42	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
43	Illinois Valley Hospital	Peru	Illinois	United States	61354
44	Perry Memorial Hospital	Princeton	Illinois	United States	61356
45	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
46	Carle Clinic-Urbana Main	Urbana	Illinois	United States	61801
47	Carle Foundation dba Carle Cancer Center	Urbana	Illinois	United States	61801
48	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
49	Saint Anthony Memorial Health Center	Michigan City	Indiana	United States	46360
50	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
51	McFarland Clinic	Ames	Iowa	United States	50010
52	Saint Luke's Hospital	Cedar Rapids	Iowa	United States	52402
53	Cedar Rapids Oncology Association	Cedar Rapids	Iowa	United States	52403
54	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
55	Oncology Associates	Cedar Rapids	Iowa	United States	52403
56	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
57	Mercy Capitol	Des Moines	Iowa	United States	50307
58	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
59	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
60	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
61	Medical Oncology and Hematology Associates	Des Moines	Iowa	United States	50314
62	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
63	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
64	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
65	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101-1733
66	Siouxland Hematology - Oncology Associates	Sioux City	Iowa	United States	51101
67	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
68	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
69	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
70	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
71	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
72	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
73	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
74	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
75	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
76	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
77	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
78	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
79	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
80	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
81	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
82	Associates In Womens Health	Wichita	Kansas	United States	67208
83	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
84	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
85	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
86	Wichita CCOP	Wichita	Kansas	United States	67214
87	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
88	Bixby Medical Center	Adrian	Michigan	United States	49221
89	Hickman Cancer Center	Adrian	Michigan	United States	49221
90	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
91	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
92	Oakwood Hospital	Dearborn	Michigan	United States	48123
93	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
94	Hurley Medical Center	Flint	Michigan	United States	48502
95	Genesys Regional Medical Center	Flint	Michigan	United States	48532
96	Allegiance Health	Jackson	Michigan	United States	49201
97	Sparrow Hospital	Lansing	Michigan	United States	48912
98	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
99	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
100	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
101	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
102	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
103	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
104	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
105	Merit Care Clinic Bemidji	Bemidji	Minnesota	United States	56601
106	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
107	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
108	Duluth Clinic CCOP	Duluth	Minnesota	United States	55805
109	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
110	Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
111	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
112	Unity Hospital	Fridley	Minnesota	United States	55432
113	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
114	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
115	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
116	Mayo Clinic	Rochester	Minnesota	United States	55905
117	Metro-Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
118	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
119	United Hospital	Saint Paul	Minnesota	United States	55102
120	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
121	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
122	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
123	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59101
124	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
125	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
126	Saint Vincent Healthcare	Billings	Montana	United States	59101
127	Billings Clinic	Billings	Montana	United States	59107-7000
128	Deaconess Medical Center	Billings	Montana	United States	59107
129	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
130	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
131	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
132	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
133	Great Falls Clinic	Great Falls	Montana	United States	59405
134	Northern Montana Hospital	Havre	Montana	United States	59501
135	Saint Peter's Community Hospital	Helena	Montana	United States	59601
136	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
137	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
138	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
139	Community Medical Hospital	Missoula	Montana	United States	59801
140	Montana Cancer Specialists	Missoula	Montana	United States	59802
141	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
142	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
143	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
144	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
145	Medcenter One Health Systems	Bismarck	North Dakota	United States	58501
146	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
147	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
148	Meritcare Hospital	Fargo	North Dakota	United States	58122
149	MeritCare Medical Group	Fargo	North Dakota	United States	58122
150	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
151	Grandview Hospital	Dayton	Ohio	United States	45405
152	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
153	Miami Valley Hospital	Dayton	Ohio	United States	45409
154	Samaritan North Health Center	Dayton	Ohio	United States	45415
155	Veteran Affairs Medical Center	Dayton	Ohio	United States	45428
156	Dayton CCOP	Dayton	Ohio	United States	45429
157	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
158	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
159	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
160	Fremont Memorial Hospital	Fremont	Ohio	United States	43420
161	Wayne Hospital	Greenville	Ohio	United States	45331
162	Cole, Sharon, K. M.D. (UIA Investigator)	Kenton	Ohio	United States	43326
163	Kettering Medical Center	Kettering	Ohio	United States	45429
164	Lima Memorial Hospital	Lima	Ohio	United States	45804
165	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
166	Saint Luke's Hospital	Maumee	Ohio	United States	43537
167	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
168	Bayview Oncology Associates	Oregon	Ohio	United States	43616
169	Saint Charles Hospital	Oregon	Ohio	United States	43616
170	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
171	North Coast Cancer Care	Sandusky	Ohio	United States	44870
172	Flower Memorial Hospital	Sylvania	Ohio	United States	43560
173	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
174	The Toledo Hospital	Toledo	Ohio	United States	43606
175	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
176	University of Toledo	Toledo	Ohio	United States	43614
177	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
178	Mercy Cancer Center at Saint Anne Mercy Hospital	Toledo	Ohio	United States	43623
179	Stark, Michael, Edward. M.D. (UIA Investigator)	Toledo	Ohio	United States	43623
180	Toledo Clinic	Toledo	Ohio	United States	43623
181	Upper Valley Medical Center	Troy	Ohio	United States	45373
182	Fulton County Health Center	Wauseon	Ohio	United States	43567
183	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
184	Greene Memorial Hospital	Xenia	Ohio	United States	45385
185	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
186	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
187	Geisinger Medical Group	State College	Pennsylvania	United States	16801
188	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania	United States	18711
189	AnMed Health Hospital	Anderson	South Carolina	United States	29621
190	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
191	Upstate Carolina CCOP	Spartanburg	South Carolina	United States	29303
192	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
193	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota	United States	57105
194	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
195	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephen Ansell, North Central Cancer Treatment Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00109967
• Other Study ID Numbers: NCI-2009-00644; N038H; U10CA025224; CDR0000425334
• First Posted: May 4, 2005
• Last Update Posted: Apr 17, 2014
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Sirolimus; Rituximab

Study Results

Participant Flow

Recruitment Details	Seventy-one patients seen at 35 sites were enrolled on this trial between May 6, 2005 and March 6, 2009. Two patients canceled before receiving treatment and 69 patients were therefore included in the analysis. There were 48 patients in group 1 (rituximab-sensitive) and 21 (rituximab-refractory) in group 2.
Pre-assignment Detail	The patients were stratified by their previous response to rituximab into rituximab sensitive (group 1) or rituximab refractory (group 2) groups. Rituximab refractory was defined as no response (stable disease or progression) or a response that lasted <6 months the last time the patient received rituximab alone or rituximab with chemotherapy.

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	50	21
COMPLETED	30	15
NOT COMPLETED	20	6

Baseline Characteristics

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	48	21	69
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.5	66	67
Sex: Female, Male (Count of Participants)
Female	13 27.1%	6 28.6%	19 27.5%
Male	35 72.9%	15 71.4%	50 72.5%
Region of Enrollment (participants) [Number]
United States	48 100%	21 100%	69 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria
Description	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.
Time Frame	Up to 12, 28-day cycles.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Measure Participants	48	21
Number (95% Confidence Interval) [percentage of patients]	62.5	52.4

2. Secondary Outcome

Title	Time to Progression
Description	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.
Time Frame	Patients were followed up to five years after registration.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Measure Participants	48	21
Median (95% Confidence Interval) [months]	10.9	5.4

3. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	Response duration is followed up to 5 years from registration.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Measure Participants	30	11
Median (95% Confidence Interval) [months]	11.0	6.6

4. Secondary Outcome

Title	Toxicity
Description	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.
Time Frame	Assessed during treatment (up to 12, 28-day cycles)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Measure Participants	48	21
Grade 3 or Higher	36	17
Grade 4 or Higher	7	2

5. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	Patients were followed for survival status for up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I: Rituximab Sensitive	Group II: Rituximab Refractory
Arm/Group Description	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	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
Measure Participants	48	21
Median (95% Confidence Interval) [months]	32.6	24.2

Adverse Events

Arm/Group Title	Group I: Rituximab Sensitive		Group II: Rituximab Refractory
Arm/Group Description	temsirolimus: 25 mg given IV		temsirolimus: 25 mg given IV
All Cause Mortality
	Group I: Rituximab Sensitive		Group II: Rituximab Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group I: Rituximab Sensitive		Group II: Rituximab Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/48 (33.3%)		7/21 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/48 (2.1%)	1	0/21 (0%)	0
Hemoglobin decreased	1/48 (2.1%)	1	0/21 (0%)	0
Cardiac disorders
Left ventricular failure	0/48 (0%)	0	1/21 (4.8%)	1
Myocardial ischemia	1/48 (2.1%)	1	0/21 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/48 (2.1%)	1	0/21 (0%)	0
Hemorrhoids	1/48 (2.1%)	1	0/21 (0%)	0
Rectal pain	1/48 (2.1%)	1	0/21 (0%)	0
General disorders
Death NOS	0/48 (0%)	0	1/21 (4.8%)	1
Disease progression	1/48 (2.1%)	1	0/21 (0%)	0
Fever	1/48 (2.1%)	1	0/21 (0%)	0
Localized edema	0/48 (0%)	0	1/21 (4.8%)	1
Immune system disorders
Hypersensitivity	1/48 (2.1%)	1	0/21 (0%)	0
Infections and infestations
Catheter related infection	2/48 (4.2%)	2	0/21 (0%)	0
Pneumonia	4/48 (8.3%)	4	1/21 (4.8%)	1
Skin infection	1/48 (2.1%)	1	0/21 (0%)	0
Soft tissue infection	1/48 (2.1%)	1	0/21 (0%)	0
Investigations
Aspartate aminotransferase increased	0/48 (0%)	0	1/21 (4.8%)	1
Leukocyte count decreased	0/48 (0%)	0	1/21 (4.8%)	1
Neutrophil count decreased	3/48 (6.3%)	5	1/21 (4.8%)	1
Platelet count decreased	3/48 (6.3%)	5	2/21 (9.5%)	2
Metabolism and nutrition disorders
Dehydration	0/48 (0%)	0	1/21 (4.8%)	1
Serum calcium decreased	1/48 (2.1%)	1	0/21 (0%)	0
Nervous system disorders
Encephalopathy	0/48 (0%)	0	1/21 (4.8%)	1
Peripheral sensory neuropathy	1/48 (2.1%)	1	0/21 (0%)	0
Tremor	1/48 (2.1%)	1	0/21 (0%)	0
Renal and urinary disorders
Renal failure	0/48 (0%)	0	2/21 (9.5%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/48 (2.1%)	3	1/21 (4.8%)	1
Hypoxia	1/48 (2.1%)	1	0/21 (0%)	0
Pleural effusion	0/48 (0%)	0	1/21 (4.8%)	1
Pneumonitis	4/48 (8.3%)	5	1/21 (4.8%)	1
Vascular disorders
Hematoma	1/48 (2.1%)	1	0/21 (0%)	0
Hemorrhage	1/48 (2.1%)	1	0/21 (0%)	0
Thrombosis	1/48 (2.1%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Group I: Rituximab Sensitive		Group II: Rituximab Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/48 (100%)		21/21 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	29/48 (60.4%)	143	16/21 (76.2%)	88
Hemolysis	0/48 (0%)	0	1/21 (4.8%)	2
Cardiac disorders
Left ventricular dysfunction	2/48 (4.2%)	2	0/21 (0%)	0
Pericardial effusion	1/48 (2.1%)	1	0/21 (0%)	0
Sinus tachycardia	1/48 (2.1%)	1	0/21 (0%)	0
Ventricular tachycardia	1/48 (2.1%)	1	0/21 (0%)	0
Ear and labyrinth disorders
External ear pain	1/48 (2.1%)	1	0/21 (0%)	0
Endocrine disorders
Endocrine disorder	1/48 (2.1%)	1	0/21 (0%)	0
Hypothyroidism	1/48 (2.1%)	1	0/21 (0%)	0
Eye disorders
Dry eye syndrome	1/48 (2.1%)	2	1/21 (4.8%)	9
Eye disorder	1/48 (2.1%)	1	0/21 (0%)	0
Eye pain	1/48 (2.1%)	1	0/21 (0%)	0
Photophobia	1/48 (2.1%)	3	0/21 (0%)	0
Watering eyes	1/48 (2.1%)	4	1/21 (4.8%)	3
Gastrointestinal disorders
Abdominal distension	1/48 (2.1%)	2	0/21 (0%)	0
Abdominal pain	1/48 (2.1%)	1	0/21 (0%)	0
Anal exam abnormal	1/48 (2.1%)	1	0/21 (0%)	0
Constipation	6/48 (12.5%)	21	4/21 (19%)	9
Diarrhea	16/48 (33.3%)	51	6/21 (28.6%)	10
Dry mouth	2/48 (4.2%)	3	1/21 (4.8%)	5
Dyspepsia	3/48 (6.3%)	6	0/21 (0%)	0
Dysphagia	0/48 (0%)	0	1/21 (4.8%)	1
Ear, nose and throat examination abnormal	1/48 (2.1%)	3	3/21 (14.3%)	4
Esophageal mucositis	0/48 (0%)	0	1/21 (4.8%)	1
Esophagitis	0/48 (0%)	0	1/21 (4.8%)	1
Flatulence	1/48 (2.1%)	1	0/21 (0%)	0
Gastric mucositis	1/48 (2.1%)	1	0/21 (0%)	0
Gastroscopy abnormal	1/48 (2.1%)	1	0/21 (0%)	0
Gingival pain	1/48 (2.1%)	1	0/21 (0%)	0
Hemorrhoids	0/48 (0%)	0	1/21 (4.8%)	1
Mucositis oral	19/48 (39.6%)	47	5/21 (23.8%)	5
Nausea	11/48 (22.9%)	20	10/21 (47.6%)	25
Oral pain	1/48 (2.1%)	1	1/21 (4.8%)	2
Rectal hemorrhage	0/48 (0%)	0	1/21 (4.8%)	1
Vomiting	3/48 (6.3%)	4	1/21 (4.8%)	2
General disorders
Chest pain	2/48 (4.2%)	4	0/21 (0%)	0
Chills	2/48 (4.2%)	3	1/21 (4.8%)	1
Disease progression	0/48 (0%)	0	1/21 (4.8%)	1
Edema limbs	14/48 (29.2%)	50	5/21 (23.8%)	18
Fatigue	36/48 (75%)	170	16/21 (76.2%)	74
Fever	4/48 (8.3%)	5	1/21 (4.8%)	1
Localized edema	1/48 (2.1%)	8	0/21 (0%)	0
Pain	3/48 (6.3%)	3	0/21 (0%)	0
Immune system disorders
Hypersensitivity	3/48 (6.3%)	4	1/21 (4.8%)	1
Infections and infestations
Bladder infection	0/48 (0%)	0	1/21 (4.8%)	1
Bronchitis	1/48 (2.1%)	1	1/21 (4.8%)	1
Eye infection	1/48 (2.1%)	1	1/21 (4.8%)	1
Gingival infection	1/48 (2.1%)	1	1/21 (4.8%)	1
Infection	3/48 (6.3%)	3	1/21 (4.8%)	1
Nail infection	1/48 (2.1%)	3	0/21 (0%)	0
Pneumonia	3/48 (6.3%)	3	2/21 (9.5%)	3
Sinusitis	2/48 (4.2%)	4	2/21 (9.5%)	2
Skin infection	0/48 (0%)	0	2/21 (9.5%)	2
Small intestine infection	0/48 (0%)	0	1/21 (4.8%)	1
Upper respiratory infection	2/48 (4.2%)	2	2/21 (9.5%)	2
Urinary tract infection	1/48 (2.1%)	1	0/21 (0%)	0
Injury, poisoning and procedural complications
Bruising	1/48 (2.1%)	2	0/21 (0%)	0
Vascular access complication	1/48 (2.1%)	1	0/21 (0%)	0
Wound dehiscence	1/48 (2.1%)	2	0/21 (0%)	0
Investigations
Alanine aminotransferase increased	2/48 (4.2%)	2	2/21 (9.5%)	4
Alkaline phosphatase increased	7/48 (14.6%)	25	6/21 (28.6%)	7
Aspartate aminotransferase increased	4/48 (8.3%)	8	4/21 (19%)	7
Creatinine increased	6/48 (12.5%)	30	5/21 (23.8%)	16
INR increased	5/48 (10.4%)	19	0/21 (0%)	0
Laboratory test abnormal	0/48 (0%)	0	1/21 (4.8%)	2
Leukocyte count decreased	28/48 (58.3%)	174	16/21 (76.2%)	68
Lipase increased	0/48 (0%)	0	1/21 (4.8%)	1
Lymphocyte count decreased	7/48 (14.6%)	64	3/21 (14.3%)	20
Neutrophil count decreased	21/48 (43.8%)	97	13/21 (61.9%)	38
Platelet count decreased	34/48 (70.8%)	176	15/21 (71.4%)	75
Serum cholesterol increased	35/48 (72.9%)	136	15/21 (71.4%)	45
Weight loss	13/48 (27.1%)	27	7/21 (33.3%)	26
Metabolism and nutrition disorders
Anorexia	13/48 (27.1%)	27	9/21 (42.9%)	22
Blood bicarbonate decreased	1/48 (2.1%)	1	0/21 (0%)	0
Blood glucose increased	21/48 (43.8%)	45	11/21 (52.4%)	38
Dehydration	1/48 (2.1%)	3	0/21 (0%)	0
Serum albumin decreased	6/48 (12.5%)	12	2/21 (9.5%)	2
Serum calcium decreased	8/48 (16.7%)	28	2/21 (9.5%)	2
Serum calcium increased	0/48 (0%)	0	2/21 (9.5%)	2
Serum glucose decreased	2/48 (4.2%)	7	0/21 (0%)	0
Serum magnesium decreased	1/48 (2.1%)	1	0/21 (0%)	0
Serum phosphate decreased	1/48 (2.1%)	2	0/21 (0%)	0
Serum potassium decreased	4/48 (8.3%)	6	4/21 (19%)	7
Serum potassium increased	1/48 (2.1%)	1	1/21 (4.8%)	1
Serum sodium decreased	5/48 (10.4%)	9	2/21 (9.5%)	5
Serum sodium increased	1/48 (2.1%)	1	1/21 (4.8%)	6
Serum triglycerides increased	37/48 (77.1%)	151	16/21 (76.2%)	63
Musculoskeletal and connective tissue disorders
Arthralgia	7/48 (14.6%)	19	1/21 (4.8%)	1
Arthritis	1/48 (2.1%)	1	0/21 (0%)	0
Back pain	5/48 (10.4%)	14	1/21 (4.8%)	1
Chest wall pain	0/48 (0%)	0	1/21 (4.8%)	1
Muscle weakness	2/48 (4.2%)	6	3/21 (14.3%)	3
Muscle weakness lower limb	1/48 (2.1%)	3	1/21 (4.8%)	1
Muscle weakness upper limb	1/48 (2.1%)	2	0/21 (0%)	0
Myalgia	5/48 (10.4%)	8	1/21 (4.8%)	2
Neck pain	2/48 (4.2%)	2	0/21 (0%)	0
Pain in extremity	4/48 (8.3%)	4	1/21 (4.8%)	1
Nervous system disorders
Dizziness	5/48 (10.4%)	15	2/21 (9.5%)	2
Dysgeusia	12/48 (25%)	30	2/21 (9.5%)	6
Headache	6/48 (12.5%)	8	2/21 (9.5%)	2
Peripheral motor neuropathy	4/48 (8.3%)	6	2/21 (9.5%)	2
Peripheral sensory neuropathy	12/48 (25%)	41	5/21 (23.8%)	17
Syncope	1/48 (2.1%)	1	0/21 (0%)	0
Tremor	0/48 (0%)	0	1/21 (4.8%)	1
Psychiatric disorders
Anxiety	3/48 (6.3%)	10	0/21 (0%)	0
Confusion	1/48 (2.1%)	6	1/21 (4.8%)	1
Depression	2/48 (4.2%)	7	0/21 (0%)	0
Insomnia	4/48 (8.3%)	7	2/21 (9.5%)	3
Renal and urinary disorders
Urinary frequency	2/48 (4.2%)	9	0/21 (0%)	0
Reproductive system and breast disorders
Reproductive tract disorder	1/48 (2.1%)	4	0/21 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/48 (6.3%)	7	3/21 (14.3%)	3
Apnea	0/48 (0%)	0	1/21 (4.8%)	1
Cough	9/48 (18.8%)	13	3/21 (14.3%)	12
Dyspnea	8/48 (16.7%)	14	5/21 (23.8%)	9
Epistaxis	4/48 (8.3%)	14	2/21 (9.5%)	6
Hypoxia	1/48 (2.1%)	1	0/21 (0%)	0
Laryngoscopy abnormal	1/48 (2.1%)	1	0/21 (0%)	0
Pharyngolaryngeal pain	1/48 (2.1%)	3	3/21 (14.3%)	4
Pleural effusion	1/48 (2.1%)	1	0/21 (0%)	0
Pneumonitis	9/48 (18.8%)	15	1/21 (4.8%)	1
Pulmonary hypertension	0/48 (0%)	0	1/21 (4.8%)	2
Respiratory disorder	4/48 (8.3%)	7	1/21 (4.8%)	1
Voice alteration	2/48 (4.2%)	4	0/21 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/48 (4.2%)	2	1/21 (4.8%)	12
Dry skin	1/48 (2.1%)	1	1/21 (4.8%)	12
Hand-and-foot syndrome	1/48 (2.1%)	1	0/21 (0%)	0
Nail disorder	10/48 (20.8%)	31	3/21 (14.3%)	13
Pain of skin	1/48 (2.1%)	1	0/21 (0%)	0
Petechiae	0/48 (0%)	0	1/21 (4.8%)	2
Pruritus	6/48 (12.5%)	15	3/21 (14.3%)	10
Rash acneiform	3/48 (6.3%)	5	1/21 (4.8%)	1
Rash desquamating	26/48 (54.2%)	88	12/21 (57.1%)	40
Skin atrophy	1/48 (2.1%)	2	0/21 (0%)	0
Skin disorder	1/48 (2.1%)	7	0/21 (0%)	0
Skin hyperpigmentation	1/48 (2.1%)	9	0/21 (0%)	0
Sweating	1/48 (2.1%)	1	0/21 (0%)	0
Urticaria	2/48 (4.2%)	4	0/21 (0%)	0
Vascular disorders
Flushing	0/48 (0%)	0	1/21 (4.8%)	1
Hemorrhage	1/48 (2.1%)	1	0/21 (0%)	0
Hot flashes	1/48 (2.1%)	1	0/21 (0%)	0
Hypertension	2/48 (4.2%)	6	0/21 (0%)	0
Hypotension	2/48 (4.2%)	2	0/21 (0%)	0
Phlebitis	1/48 (2.1%)	1	0/21 (0%)	0
Thrombosis	3/48 (6.3%)	3	1/21 (4.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.