Phase I/II Trial of VELCADE + CHOP-Rituximab in Untreated DLCBL or Mantle Cell NHL

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00151320
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 76
• Locations: 4
• Arm: 1
• Actual Duration (Months): 111.7
• Patients Per Site: 19
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary Objective:

To determine the toxicity profile and maximum tolerated dose (MTD) of VELCADE when administered in combination with CHOP + Rituximab to patients with previously untreated diffuse large B cell or mantle cell non-Hodgkin's lymphoma (NHL)

Secondary Objectives:

To assess the response rate (overall and complete), event-free survival and overall survival with VELCADE and CHOP-R in patients with previously untreated diffuse large B cell or mantle cell lymphoma (phase II component)

Treatment:

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles

Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications)

VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of

VELCADE will be determined by the following dose escalation schedule:

Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Bortezomib, CHOP, Rituximab	Phase 1/Phase 2

Detailed Description

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles

Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications)

VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of

VELCADE will be determined by the following dose escalation schedule:

Once completed six cycles of therapy (~18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the dose escalation schedule.Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the dose escalation schedule.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of VELCADE+ CHOP-Rituximab in Patients With Previously Untreated Diffuse Large B Cell or Mantle Cell Non-Hodgkin's Lymphoma
• Actual Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 24, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1 Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by a dose escalation schedule.

Drug: Bortezomib, CHOP, Rituximab; Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4; Other Names: VELCADE

Outcome Measures

Primary Outcome Measures

1. ORR [6 cycles (18 weeks)]

   Overall Response Rate

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed diagnosis of diffuse large B cell or mantle cell

Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles. For mantle cell:

CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-).

• Patient has not received any prior anti-cancer therapy for lymphoma

• Tumor tissue confirmed to express the CD20 antigen

• Available frozen tumor tissue(rebiopsy if needed)

• Patient has measurable disease as defined by a tumor mass > 1.5 cm

• Patient has Stage II, III, or IV disease

• Age > 18 years

• Absolute granulocyte count > 1000 cells/mm3

• Platelet count > 50,000 cells/mm3

• Creatinine < 2.0 x ULN

• Total bilirubin < 2.0 x ULN

Exclusion Criteria:

• Known central nervous system (CNS) involvement by lymphoma

• Known HIV disease

• Patient is pregnant or nursing

• Patient has had major surgery within the last 3 weeks

• Patient is receiving other investigational drugs

• Known peripheral neuropathy > Grade 2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Nebraska Medical Center	Omaha	Nebraska	United States	68198
3	Weill Medical College of Cornell University	New York	New York	United States	10021
4	Columbia University College of Physicians and Surgeons	New York	New York	United States	10032

Sponsors and Collaborators

• Weill Medical College of Cornell University
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: John P Leonard, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00151320
• Other Study ID Numbers: 0309006313
• First Posted: Sep 8, 2005
• Last Update Posted: Jun 19, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Weill Medical College of Cornell University: diffuse large B cell; mantle cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Arm 1
Arm/Group Description	Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by a dose escalation schedule. Bortezomib, CHOP, Rituximab: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4
Period Title: Overall Study
STARTED	76
COMPLETED	76
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Untreated DLBCL	Untreated MCL	Total
Arm/Group Description	with untreated Diffuse Large B-cell Lymphoma (n = 40)	with untreated mantle cell Non-Hodgkin's Lymphoma	Total of all reporting groups
Overall Participants	40	36	76
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	66	63
Sex: Female, Male (Count of Participants)
Female	13 32.5%	6 16.7%	19 25%
Male	27 67.5%	30 83.3%	57 75%

Outcome Measures

1. Primary Outcome

Title	ORR
Description	Overall Response Rate
Time Frame	6 cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Untreated DLBCL	Untreated MCL
Arm/Group Description	with untreated Diffuse Large B-cell Lymphoma (n = 40)	with untreated mantle cell Non-Hodgkin's Lymphoma
Measure Participants	40	36
Number [percentage of patients]	88	81

Adverse Events

Arm/Group Title	Arm 1
Arm/Group Description	Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by a dose escalation schedule. Bortezomib, CHOP, Rituximab: Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications) VELCADE (Bortezomib) is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of VELCADE will be determined by the following dose escalation schedule: Level Dose/Schedule (-2) 0.7 mg/m2 on day 1 of each cycle (-1) 0.7 mg/m2 on days 1 and 8 (0) 0.7 mg/m2 on days 1 and 4 (+1) 1.0 mg/m2 on days 1 and 4 (+2) 1.3 mg/m2 on days 1 and 4
All Cause Mortality
	Arm 1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm 1
	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)
Renal and urinary disorders
Uroepithelial carcinoma	1/76 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Arm 1
	Affected / at Risk (%)	# Events
Total	76/76 (100%)
Blood and lymphatic system disorders
Neutropenia	42/76 (55.3%)
Anemia	60/76 (78.9%)
Thrombocytopenia	59/76 (77.6%)
Deep Vein Thrombosis	2/76 (2.6%)
Cardiac disorders
Cardiac Arrhythmia	6/76 (7.9%)
Congestive heart failure	2/76 (2.6%)
Gastrointestinal disorders
Anorexia	31/76 (40.8%)
Constipation	37/76 (48.7%)
Diarrhea	25/76 (32.9%)
General disorders
Nausea	33/76 (43.4%)
Edema	18/76 (23.7%)
Vomiting	14/76 (18.4%)
Infections and infestations
Febrile Neutropenia	13/76 (17.1%)
Infection (normal ANC)	14/76 (18.4%)
Sepsis	6/76 (7.9%)
Nervous system disorders
Neuropathy	49/76 (64.5%)
Renal and urinary disorders
acute renal failure	2/76 (2.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	18/76 (23.7%)
Pleural effusion	6/76 (7.9%)
Interstitial pneumonitis	2/76 (2.6%)

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.