Bortezomib Plus CHOP Every 2 Weeks for Advanced Stage DLBCL

• Sponsor: Asan Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00379574
• Collaborator: Janssen Korea, Ltd., Korea (Industry)
• Enrollment: 49
• Locations: 2
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 24.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Diffuse large B-cell lymphoma is a most prevalent non-Hodgkin's lymphoma. Recently the clinical results have been improved with new drugs and new modalities such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks. Bortezomib is well known to be effective for multiple myeloma and has been being tried for other malignancies including lymphoma. The investigators will incorporate Bortezomib to CHOP every 2 weeks to further improve the clinical efficacy in diffuse large B-cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large-Cell, Diffuse; Lymphoma, B-Cell	Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone; Drug: Lenograstim	Phase 1/Phase 2

Detailed Description

Intended number of patients: 63 patients in total

• Phase I: 9 patients for 3 levels

• Phase II: 50 patients plus 3 patient from Phase I at MTD level

• Plus 4 patients: considering 5% follow-up loss rate

Study design and methodology:

For phase I, 9 patients; 3 levels of bortezomib (1.0, 1.3 and 1.6 mg/m2), 3 patients at each dose level.

If escalation of bortezomib beyond 1.0 mg/m2 is not possible, the trial will be stopped.

For phase II, 53 patients (3 from phase I at MTD level); Reject when complete response rate equal or less than 12/19 or 37/53 by Simon two-stage optimal phase II design.

Treatments:

• Bortezomib:

For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks.

For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks.

• CHOP2: cyclophosphamide 750mg/ m2 day 1, vincristine 1.4 mg/ m2 (max. 2 mg) day 1, doxorubicin 50 mg/ m2 day 1, prednisolone 100 mg days 1-5, every 2 weeks.

• G-CSF: Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bortezomib + CHOP every 2 weeks Bortezomib + CHOP(Cycloophosphamide, vincristine, doxorubicin,and predinisolone) every 2 weeks

Drug: Bortezomib; Bortezomib: For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks. For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks.; Other Names: velcade ; Drug: Cyclophosphamide; cyclophosphamide 750mg/m2 day 1, every 2 weeks; Other Names: cytoxan ; Drug: Doxorubicin; doxorubicin 50 mg/m2 day 1, every 2 weeks; Other Names: adriamycin ; Drug: Vincristine; vincristine 1.4 mg/m2 (max. 2 mg) day 1, every 2 weeks; Other Names: Oncovin ; Drug: Prednisolone; prednisolone 100 mg days 1-5, every 2 weeks; Other Names: Pd ; Drug: Lenograstim; Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks; Other Names: Neutrogin G-CSF

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Achieved Complete Response [14 weeks]

   All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms.

Secondary Outcome Measures

1. Number of Patients Who Experienced Adverse Events [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed DLBCL

• Age 70 years or less

• Previously untreated

• Performance status: ECOG 0-2

• Advanced stage: stage III, IV, or non-contiguous stage II

• Measurable disease: 1 cm or more by spiral CT

• Normal liver function

Exclusion Criteria:

• Platelet count less than 75,000/microL within 14 days before enrollment.

• Absolute neutrophil count of less than 1,500/microlL within 14 days before enrollment.

• Cr more than 2.0 mg/dL and/or calculated or measured creatinine clearance less than 50 mL/min within 14 days before enrollment.

• Peripheral neuropathy of Grade 2 or worse within 14 days before enrollment.

• Hypersensitivity to bortezomib, boron or mannitol.

• Female subject is pregnant or breast-feeding.

• Other investigational drugs with 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• Uncontrolled or severe cardiovascular disease, including MI within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center, University of Ulsan College of Medicine	Seoul		Korea, Republic of	138-736
2	Asan Medical Cener	Seoul		Korea, Republic of

Sponsors and Collaborators

• Asan Medical Center
• Janssen Korea, Ltd., Korea

Investigators

• Principal Investigator: Cheolwon Suh, M.D.,Ph.D., Asan Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cheolwon Suh, Professor, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT00379574
• Other Study ID Numbers: AMC 2006-276
• First Posted: Sep 22, 2006
• Last Update Posted: Mar 15, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Cheolwon Suh, Professor, Asan Medical Center: diffuse large B-cell lymphoma; Bortezomib; CHOP; Lenograstim
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Prednisolone; Cyclophosphamide; Doxorubicin; Vincristine; Bortezomib; Lenograstim

Study Results

Participant Flow

Recruitment Details	Duration of patient enrollment: From 15-Dec-2006 to 02-May-2009

Arm/Group Title	Bortezomib + CHOP Every 2 Weeks
Arm/Group Description	Phase I Bortezomib 1.0, 1/3, and 1.6 mg/m2 CHOP,every 2 weeks cyclophosphamide 750 mg/m2 D1 doxorubicin 50 mg/m2 D1 vincristine 1.4 mg/m2 D1 prednisone 100 mg D1-D5 Phase II Bortezomib 1.6 mg/m2 CHOP,every 2 weeks cyclophosphamide 750 mg/m2 D1 doxorubicin 50 mg/m2 D1 vincristine 1.4 mg/m2 D1 prednisone 100 mg D1-D5
Period Title: Overall Study
STARTED	49
COMPLETED	49
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bortezomib + CHOP Every 2 Weeks
Arm/Group Description	CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone
Overall Participants	49
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	42 85.7%
>=65 years	7 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (10)
Sex: Female, Male (Count of Participants)
Female	25 51%
Male	24 49%
Region of Enrollment (participants) [Number]
Korea, Republic of	49 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Achieved Complete Response
Description	All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms.
Time Frame	14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib + CHOP Every 2 Weeks
Arm/Group Description	CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone
Measure Participants	49
Number [participants]	32 65.3%

2. Secondary Outcome

Title	Number of Patients Who Experienced Adverse Events
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib + CHOP Every 2 Weeks
Arm/Group Description	CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone
Measure Participants	49
Number [participants]	49 100%

Adverse Events

Arm/Group Title	Bortezomib + CHOP Every 2 Weeks
Arm/Group Description	CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone
All Cause Mortality
	Bortezomib + CHOP Every 2 Weeks
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bortezomib + CHOP Every 2 Weeks
	Affected / at Risk (%)	# Events
Total	22/49 (44.9%)
Blood and lymphatic system disorders
anemia	22/40 (55%)	22
neutropenia	14/40 (35%)	14
feberile neutropenia	7/40 (17.5%)	15
thrombocytopenia	13/40 (32.5%)	13
Endocrine disorders
hyperglycemia	4/40 (10%)	4
Gastrointestinal disorders
abdominal pain	4/40 (10%)	4
constipation	0/40 (0%)	0
diarrhea	4/40 (10%)	4
vomiting	4/40 (10%)	4
Metabolism and nutrition disorders
fatigue	2/40 (5%)	2
Nervous system disorders
sensory neuropathy	11/40 (27.5%)	11
motor neuropathy	3/40 (7.5%)	3
Other (Not Including Serious) Adverse Events
	Bortezomib + CHOP Every 2 Weeks
	Affected / at Risk (%)	# Events
Total	27/49 (55.1%)
Blood and lymphatic system disorders
anemia	11/40 (27.5%)	19
neutropenia	12/40 (30%)	15
thrombocytopenia	15/40 (37.5%)	17
Gastrointestinal disorders
abdominal pain	27/40 (67.5%)	27
anorexia	25/40 (62.5%)	26
constipation	23/40 (57.5%)	24
diarrhea	21/40 (52.5%)	22
nausea	12/40 (30%)	21
nausea	11/40 (27.5%)	20
vomiting	16/40 (40%)	20
Infections and infestations
febrile neutropenia	6/40 (15%)	7
Metabolism and nutrition disorders
fatigue	23/40 (57.5%)	25
Nervous system disorders
sensory neuropathy	22/40 (55%)	27
motor neuropathy	17/40 (42.5%)	21

Limitations/Caveats

[Not Specified]

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.