Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00460109
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 24
• Locations: 165
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: 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. Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to cancer cells. Giving rituximab together with denileukin diftitox may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with denileukin diftitox works in treating patients with previously untreated stage III or stage IV follicular B-cell non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: denileukin diftitox; Biological: rituximab	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate (complete response [CR], unconfirmed CR, and partial response) in patients with previously untreated stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with rituximab and denileukin diftitox.

• Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen.

Secondary

• Determine whether this regimen depletes or inhibits the function of regulatory T cells in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline; on day 1 of courses 2-4; and 1 and 4 months after completion of study treatment for research studies. Research studies include analysis of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD19, CD25, and CD26 by flow cytometry; quantitation of CD4+, CD25+ regulatory T cells by flow cytometry; tumor-specific γ-interferon-secreting T cells by enzyme-linked immunospot assay; tumor-specific cytotoxic T-lymphocyte activity; and immune activation by enzyme-linked immunosorbent assay.

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

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Denileukin Diftitox in Combination With Rituximab in Previously Untreated Follicular B-Cell Non-Hodgkin's Lymphoma
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rituximab + denileukin diftitox Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Biological: denileukin diftitox; Biological: rituximab

Outcome Measures

Primary Outcome Measures

1. Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response) [Up to 5 years]

   A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.

Secondary Outcome Measures

1. Survival Time [Up to 5 years]

   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

2. Time to Disease Progression [Up to 5 years]

   Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy.

3. Duration of Response [Up to 5 years]

   Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.

4. Time to Subsequent Therapy [Up to 5 years]

   Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Pathologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)

• Stage III or IV disease

• Grade 1 or 2 disease

• Previously untreated disease

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques

• Clearly defined bidimensional diameter ≥ 2 x 2 cm on physical examination OR > 2.0 cm in 1 of the dimensions by CT scan, MRI, or plain radiograph imaging

• Splenic enlargement may be used as a measurable parameter if the spleen is palpable ≥ 3 cm below the left costal margin

• Circulating tumor cells < 5,000/mm³

• Must have paraffin-embedded tissue blocks/slides available

• No CNS lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 1 year

• WBC ≥ 3,400/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 10.0 g/dL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 3 times ULN

• AST ≤ 3 times ULN

• Creatinine ≤ 1.5 times ULN

• Albumin ≥ 3 g/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 1 year after completion of study therapy

• No HIV infection

• No other active malignancies

• No active uncontrolled infection

• No known hypersensitivity to denileukin diftitox or any of its components, including diphtheria toxin, aldesleukin, or excipients

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
4	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
5	St. Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
8	St. Joseph Hospital	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	St. Mary's Regional Cancer Center at St. Mary's Hospital and 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	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	St. Mary - Corwin Regional 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	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
21	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
22	St. Anthony's Memorial Hospital	Effingham	Illinois	United States	62401
23	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
24	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
25	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
26	Elkhart General Hospital	Elkhart	Indiana	United States	46515
27	Howard Community Hospital	Kokomo	Indiana	United States	46904
28	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
29	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
30	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
31	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
32	Michiana Hematology-Oncology, PC - South Bend	South Bend	Indiana	United States	46601
33	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
34	South Bend Clinic	South Bend	Indiana	United States	46617
35	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
36	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
37	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
38	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
39	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
40	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
41	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
42	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
43	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
44	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
45	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
46	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
47	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
48	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
49	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
50	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
51	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
52	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
53	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
54	Southwest Medical Center	Liberal	Kansas	United States	67901
55	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
56	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
57	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
58	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
59	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
60	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
61	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
62	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
63	CCOP - Wichita	Wichita	Kansas	United States	67214
64	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
65	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
66	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
67	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
68	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
69	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
70	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
71	Hurley Medical Center	Flint	Michigan	United States	48503
72	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
73	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
74	Foote Memorial Hospital	Jackson	Michigan	United States	49201
75	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
76	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
77	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
78	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
79	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
80	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
81	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
82	St. John Macomb Hospital	Warren	Michigan	United States	48093
83	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
84	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
85	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
86	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
87	CCOP - Duluth	Duluth	Minnesota	United States	55805
88	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
89	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
90	Fergus Falls Medical Group, PA	Fergus Falls	Minnesota	United States	56537
91	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
92	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
93	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
94	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
95	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
96	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
97	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
98	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
99	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
100	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
101	United Hospital	Saint Paul	Minnesota	United States	55102
102	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
103	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
104	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
105	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
106	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
107	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
108	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
109	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
110	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
111	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
112	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
113	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
114	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
115		Great Falls	Montana	United States	59405
116	Northern Montana Hospital	Havre	Montana	United States	59501
117	St. Peter's Hospital	Helena	Montana	United States	59601
118	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
119	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
120	Community Medical Center	Missoula	Montana	United States	59801
121	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
122	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
123	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
124	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
125	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
126	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
127	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
128	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
129	MeritCare Broadway	Fargo	North Dakota	United States	58122
130	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
131	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
132	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
133	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
134	CCOP - Columbus	Columbus	Ohio	United States	43215
135	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
136	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
137	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
138	Grady Memorial Hospital	Delaware	Ohio	United States	43015
139	Fairfield Medical Center	Lancaster	Ohio	United States	43130
140	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
141	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
142	Mercy Medical Center	Springfield	Ohio	United States	45504
143	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
144	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
145	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
146	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
147	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
148	Adventist Medical Center	Portland	Oregon	United States	97216
149	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
150	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
151	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
152	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
153	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
154	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
155	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
156	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
157	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
158	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
159	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
160	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
161	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
162	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
163	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
164	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
165	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Stephen M. Ansell, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00460109
• Other Study ID Numbers: NCCTG-N0682; NCI-2009-00662; CDR0000539551
• First Posted: Apr 13, 2007
• Last Update Posted: Apr 18, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab; Denileukin diftitox

Study Results

Participant Flow

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	24
COMPLETED	23
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Participants	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.0
Sex: Female, Male (Count of Participants)
Female	11 47.8%
Male	12 52.2%
Region of Enrollment (participants) [Number]
United States	23 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response)
Description	A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	23
Number (95% Confidence Interval) [proportion of participants]	0.48 2.1%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	23
Median (95% Confidence Interval)	NA

3. Secondary Outcome

Title	Time to Disease Progression
Description	Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	23
Median (95% Confidence Interval)	NA

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Overall Number of Participants Analyzed reflects only the number of participants with reported data for this outcome.

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	6
Median (95% Confidence Interval) [months]	22.5

5. Secondary Outcome

Title	Time to Subsequent Therapy
Description	Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	23
Median (Full Range) [months]	NA

Adverse Events

Time Frame	Adverse events are assessed during Treatment (weekly while receiving treatment and prior to the start of a new cycle) and during Observation (1 month after completing treatment, at 4, 7, and 10 months after completing treatment, 1 year after treatment, and every 6 months for years 2-5); up to 5 years.
Adverse Event Reporting Description	This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 for adverse event monitoring and reporting. All graded adverse events are reported.
Arm/Group Title	Rituximab + Denileukin Diftitox
Arm/Group Description	Patients receive 375 mg/m^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Rituximab + Denileukin Diftitox
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab + Denileukin Diftitox
	Affected / at Risk (%)	# Events
Total	7/23 (30.4%)
Cardiac disorders
Cardiac valve disease	1/23 (4.3%)	1
Left ventricular dysfunction	1/23 (4.3%)	1
Myocardial ischemia	1/23 (4.3%)	1
Premature ventricular contractions	1/23 (4.3%)	1
Ventricular bigeminy	1/23 (4.3%)	1
Gastrointestinal disorders
Abdominal pain	1/23 (4.3%)	1
Constipation	1/23 (4.3%)	1
Dyspepsia	1/23 (4.3%)	1
Enteritis	1/23 (4.3%)	1
Nausea	1/23 (4.3%)	1
Small intestinal obstruction	1/23 (4.3%)	1
Vomiting	1/23 (4.3%)	1
General disorders
Edema limbs	1/23 (4.3%)	1
Fatigue	2/23 (8.7%)	2
Localized edema	1/23 (4.3%)	1
Immune system disorders
Cytokine release syndrome	1/23 (4.3%)	1
Investigations
Cardiac troponin I increased	1/23 (4.3%)	1
Creatine phosphokinase increased	2/23 (8.7%)	2
Metabolism and nutrition disorders
Blood glucose increased	1/23 (4.3%)	1
Dehydration	1/23 (4.3%)	1
Serum albumin decreased	1/23 (4.3%)	1
Serum calcium decreased	1/23 (4.3%)	1
Serum phosphate decreased	1/23 (4.3%)	1
Serum sodium decreased	1/23 (4.3%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	1/23 (4.3%)	1
Myalgia	1/23 (4.3%)	1
Myositis	1/23 (4.3%)	1
Nervous system disorders
Syncope	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/23 (4.3%)	1
Hypoxia	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	1/23 (4.3%)	1
Vascular disorders
Capillary leak syndrome	5/23 (21.7%)	5
Hypotension	1/23 (4.3%)	1
Thrombosis	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Rituximab + Denileukin Diftitox
	Affected / at Risk (%)	# Events
Total	22/23 (95.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	11/23 (47.8%)	26
Cardiac disorders
Cardiac pain	1/23 (4.3%)	1
Ventricular tachycardia	1/23 (4.3%)	1
Eye disorders
Retinopathy	1/23 (4.3%)	1
Gastrointestinal disorders
Constipation	1/23 (4.3%)	1
Diarrhea	1/23 (4.3%)	1
Dry mouth	1/23 (4.3%)	1
Mucositis oral	1/23 (4.3%)	1
Nausea	2/23 (8.7%)	2
Vomiting	2/23 (8.7%)	2
General disorders
Chest pain	1/23 (4.3%)	1
Chills	3/23 (13%)	3
Edema limbs	2/23 (8.7%)	2
Fatigue	3/23 (13%)	3
Pain	2/23 (8.7%)	2
Immune system disorders
Cytokine release syndrome	1/23 (4.3%)	1
Hypersensitivity	6/23 (26.1%)	7
Infections and infestations
Catheter related infection	1/23 (4.3%)	1
Wound infection	1/23 (4.3%)	1
Investigations
Activated partial thromboplastin time prolonged	1/23 (4.3%)	1
Alanine aminotransferase increased	6/23 (26.1%)	6
Aspartate aminotransferase increased	6/23 (26.1%)	6
Creatinine increased	3/23 (13%)	3
Laboratory test abnormal	1/23 (4.3%)	1
Leukocyte count decreased	3/23 (13%)	4
Lymphocyte count decreased	4/23 (17.4%)	4
Neutrophil count decreased	3/23 (13%)	3
Platelet count decreased	7/23 (30.4%)	8
Metabolism and nutrition disorders
Blood glucose increased	4/23 (17.4%)	5
Serum albumin decreased	9/23 (39.1%)	11
Serum calcium decreased	2/23 (8.7%)	2
Serum potassium decreased	1/23 (4.3%)	1
Serum potassium increased	1/23 (4.3%)	1
Serum sodium decreased	3/23 (13%)	3
Musculoskeletal and connective tissue disorders
Back pain	1/23 (4.3%)	2
Bone pain	1/23 (4.3%)	2
Muscle weakness	1/23 (4.3%)	1
Nervous system disorders
Depressed level of consciousness	1/23 (4.3%)	1
Headache	2/23 (8.7%)	3
Renal and urinary disorders
Protein urine positive	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/23 (4.3%)	1
Rash desquamating	1/23 (4.3%)	1
Vascular disorders
Capillary leak syndrome	1/23 (4.3%)	1
Flushing	1/23 (4.3%)	1
Hypertension	1/23 (4.3%)	1
Hypotension	1/23 (4.3%)	1
Thrombosis	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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