A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL

Sponsor

Seagen Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00529503

Collaborator

Genentech, Inc. (Industry)

151

Enrollment

Locations

Arms

Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin	Drug: SGN-40 Drug: placebo Drug: rituximab Drug: etoposide Drug: carboplatin Drug: ifosfamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

151 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase IIb Placebo-controlled Study of R-ICE Chemotherapy With and Without SGN-40 (Anti-CD40 Humanized Monoclonal Antibody) for Second-line Treatment of Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Study Start Date :

Sep 1, 2007

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 SGN-40, rituximab, etoposide, carboplatin, ifosfamide	Drug: SGN-40 2-8 mg/kg IV. Cycle 1: Days -1, 3, 8, 15; Cycles 2, 3: Days 1, 8, 15. Other Names: dacetuzumab Drug: rituximab 375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1 Other Names: Rituxan Drug: etoposide 100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3. Other Names: Toposar, Vepesid Drug: carboplatin AUC=5 mg/mL min IV. Cycles 1-3: Day 2. Other Names: Paraplatin Drug: ifosfamide 5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2. Other Names: Ifex
Placebo Comparator: 2 placebo, rituximab, etoposide, carboplatin, ifosfamide	Drug: placebo Volume as equivalent to corresponding SGN 40 dose IV. Cycle 1: Days -1, 3, 8, 15. Cycles 2, 3: Days 1, 8, 15. Drug: rituximab 375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1 Other Names: Rituxan Drug: etoposide 100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3. Other Names: Toposar, Vepesid Drug: carboplatin AUC=5 mg/mL min IV. Cycles 1-3: Day 2. Other Names: Paraplatin Drug: ifosfamide 5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2. Other Names: Ifex

Arm

Intervention/Treatment

Experimental: 1

SGN-40, rituximab, etoposide, carboplatin, ifosfamide

Drug: SGN-40

2-8 mg/kg IV. Cycle 1: Days -1, 3, 8, 15; Cycles 2, 3: Days 1, 8, 15.

Other Names:

dacetuzumab

Drug: rituximab

375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1

Other Names:

Rituxan

Drug: etoposide

100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.

Other Names:

Toposar, Vepesid

Drug: carboplatin

AUC=5 mg/mL min IV. Cycles 1-3: Day 2.

Other Names:

Paraplatin

Drug: ifosfamide

5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.

Other Names:

Ifex

Placebo Comparator: 2

placebo, rituximab, etoposide, carboplatin, ifosfamide

Drug: placebo

Volume as equivalent to corresponding SGN 40 dose IV. Cycle 1: Days -1, 3, 8, 15. Cycles 2, 3: Days 1, 8, 15.

Drug: rituximab

375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1

Other Names:

Rituxan

Drug: etoposide

100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.

Other Names:

Toposar, Vepesid

Drug: carboplatin

AUC=5 mg/mL min IV. Cycles 1-3: Day 2.

Other Names:

Paraplatin

Drug: ifosfamide

5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.

Other Names:

Ifex

Outcome Measures

Primary Outcome Measures

Complete response as assessed by CT and PET scans and revised response criteria for malignant lymphoma. [9 weeks]

Secondary Outcome Measures

Adverse events, laboratory values, and anti-drug antibody immune responses. [9 weeks]
Partial response, failure free survival, overall survival, and response for one and two years following treatment. [Every 3 months for 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of de novo or transformed DLBCL, or follicular grade 3b lymphoma.
Received at least four cycles of first-line therapy with R-CHOP, or equivalent.
Best clinical response to first-line therapy of stable disease, partial response, or complete response.
At least one measureable lesion that is both greater than or equal to 1.5cm by radiographic imaging and by positive FDG-PET scan.

Exclusion Criteria:

Leptomeningeal or central nervous system lymphoma.
Received any therapy for relapsed or progressive disease except for local radiation, steroids, or rituximab.
Received a hematopoietic stem cell transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	University of California at Los Angeles	Los Angeles	California	United States	90095
3	Stanford University Medical Center	Stanford	California	United States	94305-5821
4	Christiana Care Health Systems	Newark	Delaware	United States	19718
5	Georgetown University	Washington	District of Columbia	United States	20007
6	MD Anderson Cancer Center, Orlando	Orlando	Florida	United States	32806
7	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
8	Northwestern University	Chicago	Illinois	United States	60611
9	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
10	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912
11	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
12	Park Nicollet Institute	St. Louis Park	Minnesota	United States	55416
13	Washington University School of Medicine	St. Louis	Missouri	United States	63110
14	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
15	St. Luke's Roosevelt Hospital Center	New York	New York	United States	10019
16	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
17	Ohio State University	Columbus	Ohio	United States	43210
18	Providence Portland Medical Center	Portland	Oregon	United States	97213
19	Medical University of South Carolina	Charleston	South Carolina	United States	29425
20	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
21	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
22	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4003
23	MultiCare Health System	Tacoma	Washington	United States	98405
24	West Virginia University	Morgantown	West Virginia	United States	26506-9162
25	St. Vincent's Hospital - Sydney	Darlinghurst	New South Wales	Australia	2010
26	Gosford & Wyong Hospital	Gosford	New South Wales	Australia	2250
27	Royal North Shore Hospital	St. Leonards	New South Wales	Australia	2065
28	The Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
29	St. Vincent's Hospital, Melbourne	Fitzroy	Victoria	Australia	3065
30	Royal Perth Hospital	Perth	Western Australia	Australia	6000
31	Universite de Gent	Gent		Belgium	9000
32	AZ Sint-Augustinus	Wilrijk		Belgium	2610
33	Cliniques Universitaires UCL de Mont-Goddine	Yvoir		Belgium	5530
34	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czech Republic	500 05
35	Vseobecna fakultni nemocnice v Praze	Praha 2		Czech Republic	128 08
36	Fakultni nemocnice v Motole	Praha 5		Czech Republic	150 06
37	Centre Hospitalier Andre Mignot	Le Chesnay		France	78157
38	Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes	Lyon		France	69373
39	Hopital Hotel Dieu	Nantes		France	44093
40	Groupe Hospitalier Necker - Enfants Malades	Paris		France	75743
41	Hopitaux du Haut Leveque	Pessac		France	33604
42	Centre Hospitalier Lyon Sud	Pierre Benite		France	69485
43	Centre Henri Becquerel	Rouen		France	76038
44	Hematologie CHU Purpan	Toulouse		France	31059
45	Institut Gustave-Roussy	Villejuif		France	94805
46	Johannes-Gutenberg Universitat Mainz	Mainz		Germany	55101
47	KH Maria Hilf-Franziskushaus	Monchengladbach		Germany	41063
48	Universitatsklinikum Ulm	Ulm		Germany	89081
49	Debreceni Egyetem Orvos - es Egeszsegtudomanyi Centrum	Debrecen		Hungary	H-4012
50	Petz Aladar Megyei Oktato Korhaz, IInd Department of Internal Medicine	Gyor		Hungary	H-9024
51	Kaposi Mor Oktato Korhaz	Kaposvar		Hungary
52	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikat Kozpont	Szeged		Hungary	H-6720
53	Azienda Ospedaliera Universitaria Careggi	Florence		Italy	50139
54	Azienda Ospedaliera Universitaria San Martino	Genova		Italy	16132
55	Azienda Ospedaliera Universitaria Senese	Siena		Italy	53100
56	Szpital Akademii Medycznej w Gdansku	Gdansk		Poland	80-952
57	Szpital Uniwersytecki w Krakowie	Krakow		Poland	31-501
58	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi	Lodz		Poland	93-510
59	Instytut Hematologii i Transfuzjologii	Warszawa		Poland	02-766
60	Centrum Onkologii Institut im. Marii Sklodowskiej-Curie	Warszawa		Poland	02-781
61	Samodzielny Publiczny Szpital Kliniczny Nr 1	Wroclaw		Poland	50-367
62	Hospital Clinic i Provincial	Barcelona		Spain	08036
63	Hospital de la Santa Creu i Sant Paul	Barcelona		Spain	08041
64	H. Duran y Reynals Institue Catala D'Oncologia	Barcelona		Spain
65	Hospital Ramon y Cajal	Madrid		Spain	28034
66	Hospital Universitario La Fe	Valencia		Spain	46009