Phase 2 Study of VELCADE With Fludarabine in Comparison to Rituximab With Fludarabine in Follicular Lymphoma Patients Previously Treated With Rituximab

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00850499
• Collaborator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Enrollment: 12
• Locations: 43
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a randomized, open-label, active-control, multicenter Phase 2 study of VELCADE+fludarabine in comparison with rituximab+fludarabine in subjects with relapsed advanced follicular lymphoma. Eligible subjects will be randomized in a 1:1 ratio between the 2 treatment arms (55 subjects per arm).

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: fludarabine; Drug: rituximab; Drug: VELCADE	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Multicenter Phase 2 Study of VELCADE With Fludarabine in Comparison to Rituximab With Fludarabine in Follicular Lymphoma Patients Previously Treated With Rituximab
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VELCADE and fludarabine (Group A) VELCADE 1.6 mg/m2 intravenously (IV) on Days 1, 8, 15, and 22 and fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle	Drug: fludarabine; fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle; Drug: VELCADE; 1.6 mg/m2 intravenously (IV) on Days 1, 8, 15, and 22 of every 35-day cycle
Active Comparator: fludarabine and rituximab (Group B) fludarabine 40mg/m2/day orally on Days 1 to 5 and rituximab 375mg/m2 on Day 1 of every 35-day cycle	Drug: fludarabine; fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle; Drug: rituximab; rituximab 375mg/m2 on Day 1 of every 35-day cycle

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [Up to 8 cycles (1 cycle is 35 days: 280 days)]

   The proportion of response-evaluable subjects who achieved a confirmed complete response (CR) or complete response unconfirmed (CRu). Disease response and progression were evaluated according to modified International Workshop Response Criteria (IWRC) criteria by radiographic imaging and other procedures as necessary.

Secondary Outcome Measures

1. Overall Response Rate [Up to 8 cycles (1 cycle is 35 days: 280 days)]

   The proportion of subjects who achieve CR, CRu, or partial response (PR) relative to the response evaluable population. Disease response and progression were evaluated according to the modified IWRC criteria by radiographic imaging and other procedures as necessary.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subjects 18 years or older

• Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades 1or 2 according to the World Health Organization classification

• Subjects must have received at least 12 doses (375mg/m2 or appropriately adjusted dose) of rituximab for the treatment of this lymphoma as single agent rituximab or in rituximab-containing regimens as documented in the subject's medical record

• Documented relapse or progression following last antineoplastic treatment

• At least 1 measurable tumor mass (≥1.5 cm x ≥1.0 cm)

Exclusion Criteria:

• Subjects with histological or clinical transformation to an aggressive lymphoma

• prior treatment with VELCADE or fludarabine.

• antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization

• nitrosoureas within 6 weeks before randomization

• radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization

• major surgery within 3 weeks before randomization

• chronic use of corticosteroids, such as dexamethasone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU d'Amiens	Amiens, 80		France	80054
2	Institut Bergonie	Bordeaux, 33		France	33076
3	CHU Hotel Dieu	Clermont Ferrand, 63		France	63000
4	Centre Victor Hugo	Le Mans, 72		France	72000
5	CHU Caremeau	Nimes, 30		France	30029
6	Hoptial Saint Louis	Paris Cedex 10, 75		France	75475
7	Hopital Cochin	Paris, 75, Cedex 14		France	75679
8	Klinikum Bamberg, fachbereich 3	Bamberg		Germany	BY 96049
9	Vivantes Klinikum am Urban	Berlin, BE		Germany	10967
10	Charite, group Benjamin Franklin	Berlin		Germany	BE 12203
11	Hospital Spandau	Berlin		Germany	BE 13585
12	Universitaetsklinikum Frankfurt	Frankfurt		Germany	HE 60590
13	Universitatsklinikum Gottingen, zentrum Innere medicin	Gottingen		Germany	NI 37075
14	Evangelisches Krankenhaus Hamm	Hamm		Germany	NW 50063
15	Klinikum Idar-Oberstein GmbH	Idar-Oberstein		Germany	RP 55743
16	Universitaetsklinikum Jena	Jena		Germany	TH 07740
17	Universitaetsklinikum Leipzig	Leipzig		Germany	SN 04103
18	Universitaetsklinikum Mainz	Mainz		Germany	55131
19	Robert Bosch Krankenhaus	Stuttgart		Germany	BW 70376
20	Mutterhaus der Borromaeerinnen	Trier		Germany	RP 54290
21	Universitatsklinikum Ulm	Ulm		Germany	BW 89081
22	Klinikum der Stadt Villinger-Schwenningen	Villingen-Schwenningen		Germany	78050
23	Laiko Hospital - 1st Dept. of Propaedeutic Internal Medicine	Athens		Greece	11527
24	University Hospital of Heraklion- Department of Hematology	Heraklion- Crete		Greece	71110
25	Haemek Medical Center - Hematology Department	Afula		Israel	18101
26	Rambam Med.Center - Hematology Institute	Haifa		Israel	31096
27	Hadassah University Hospital - Hematology Department	Jerusalem		Israel	91120
28	Rabin Medical Center - Hematology Institute	Petach Tikva		Israel	49100
29	Sheba MC - Hematology Institute	Ramat Gan		Israel	52621
30	Policlinico di Bari	Bari		Italy
31	Istituto Di Ematologia E Oncologia Medica - L.A. Seragnoli - Policlinico S.Orsola Malpighi	Bologna		Italy
32	Clinica di Ematologia DIMI - A.O. Ospedale S. Martino	Genova		Italy
33	Ospedale Niguarda Ca' Granda	Milano		Italy
34	Azienda Ospedaliera Antonio Cardarelli	Napoli		Italy
35	Ospedale Policlinico San Matteo Irccs	Pavia		Italy
36	A.O.Univ.Pisana-Osp. Santa Chiara	Pisa		Italy
37	Università La Sapienza, Dipartimento di Biotecnologie Cellulari ed Ematologia, Via Benevento, 6	Roma		Italy	00161
38	Azienda Ospedaliera Santa Maria di Terni	Terni		Italy
39	Divisione di Ematologia Ospedale San Bortolo - Hematology	Vicenza		Italy
40	Hospital Puerta del Mar, Secretaría de Hematología, 1ª planta	Cadiz N/a		Spain	11009
41	Hospital General Universitario Morales Meseguer, Secretaría de Hematología, 1ª planta	Murcia N/a		Spain	30008
42	Hospital Clinico Universitario Salamanca, Servicio de Hematología, 4º Planta	Salamanca		Spain	37007
43	Kantonsspital St.Gallen Department of Oncology/Hematology	St. Gallen		Switzerland	9007

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Medical Monitor, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00850499
• Other Study ID Numbers: 26866138-LYM-2033
• First Posted: Feb 25, 2009
• Last Update Posted: Dec 12, 2012
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Rituximab; Fludarabine; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Velcade + Fludarabine	Rituximab + Fludarabine
Arm/Group Description
Period Title: Overall Study
STARTED	4	8
COMPLETED	1	6
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Velcade + Fludarabine	Rituximab + Fludarabine	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	4	8	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 75%	6 75%	9 75%
>=65 years	1 25%	2 25%	3 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (12.84)	60.0 (10.06)	60.4 (10.47)
Sex: Female, Male (Count of Participants)
Female	2 50%	3 37.5%	5 41.7%
Male	2 50%	5 62.5%	7 58.3%
Region of Enrollment (participants) [Number]
France	0 0%	3 37.5%	3 25%
Greece	0 0%	1 12.5%	1 8.3%
Spain	1 25%	0 0%	1 8.3%
Israel	1 25%	0 0%	1 8.3%
Germany	0 0%	1 12.5%	1 8.3%
Switzerland	1 25%	0 0%	1 8.3%
Italy	1 25%	3 37.5%	4 33.3%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	The proportion of response-evaluable subjects who achieved a confirmed complete response (CR) or complete response unconfirmed (CRu). Disease response and progression were evaluated according to modified International Workshop Response Criteria (IWRC) criteria by radiographic imaging and other procedures as necessary.
Time Frame	Up to 8 cycles (1 cycle is 35 days: 280 days)

Outcome Measure Data

Analysis Population Description

Received at least one dose of study drug

Arm/Group Title	Velcade + Fludarabine	Rituximab + Fludarabine
Arm/Group Description	Velcade + Fludarabine	Rituximab + Fludarabine
Measure Participants	4	8
Number [participants]	2 50%	3 37.5%

2. Secondary Outcome

Title	Overall Response Rate
Description	The proportion of subjects who achieve CR, CRu, or partial response (PR) relative to the response evaluable population. Disease response and progression were evaluated according to the modified IWRC criteria by radiographic imaging and other procedures as necessary.
Time Frame	Up to 8 cycles (1 cycle is 35 days: 280 days)

Outcome Measure Data

Analysis Population Description

Received at least one dose of study drug

Arm/Group Title	Velcade + Fludarabine	Rituximab + Fludarabine
Arm/Group Description	Velcade + Fludarabine	Rituximab + Fludarabine
Measure Participants	4	8
Number [participants]	3 75%	6 75%

Adverse Events

Arm/Group Title	Velcade + Fludarabine		Rituximab + Fludarabine
Arm/Group Description
All Cause Mortality
	Velcade + Fludarabine		Rituximab + Fludarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Velcade + Fludarabine		Rituximab + Fludarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		2/8 (25%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)		0/8 (0%)
Febrile neutropenia	0/4 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Abdominal pain	1/4 (25%)		0/8 (0%)
Small Intestinal Obstruction	1/4 (25%)		0/8 (0%)
General disorders
General physical health deterioration	0/4 (0%)		1/8 (12.5%)
Pyrexia	0/4 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Dypnoea	0/4 (0%)		1/8 (12.5%)
Respiratory gas exchange disorder	0/4 (0%)		1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Velcade + Fludarabine		Rituximab + Fludarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Leukopenia	1/4 (25%)		2/8 (25%)
Lymphopenia	0/4 (0%)		2/8 (25%)
Neutropenia	1/4 (25%)		4/8 (50%)
Thrombocytopenia	1/4 (25%)		3/8 (37.5%)
Eye disorders
Blepharitis	1/4 (25%)		0/8 (0%)
Gastrointestinal disorders
Constipation	2/4 (50%)		0/8 (0%)
Diarrhoea	1/4 (25%)		0/8 (0%)
Gastrointestinal pain	1/4 (25%)		0/8 (0%)
Nausea	1/4 (25%)		1/8 (12.5%)
General disorders
Asthenia	1/4 (25%)		3/8 (37.5%)
Fatigue	0/4 (0%)		2/8 (25%)
Oedema peripheral	0/4 (0%)		1/8 (12.5%)
Performance status decreased	0/4 (0%)		1/8 (12.5%)
Infections and infestations
Nasopharyngitis	0/4 (0%)		1/8 (12.5%)
Pharyngitis	0/4 (0%)		1/8 (12.5%)
Tinea infection	0/4 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Decreased appetite	1/4 (25%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/4 (25%)		0/8 (0%)
Bone pain	1/4 (25%)		0/8 (0%)
Osteoarthritis	0/4 (0%)		1/8 (12.5%)
Nervous system disorders
Peripheral sensory neuropathy	1/4 (25%)		0/8 (0%)
Psychiatric disorders
Conversion disorder	1/4 (25%)		0/8 (0%)
Depression	1/4 (25%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/4 (0%)		1/8 (12.5%)
Cough	1/4 (25%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)		1/8 (12.5%)
Skin reaction	0/4 (0%)		1/8 (12.5%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT 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.