Bevacizumab + CHOP-Rituximab in Untreated Mantle Cell Lymphoma

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00401817
• Collaborator: (none)
• Enrollment: 11
• Locations: 2
• Arm: 1
• Actual Duration (Months): 72
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective

1. To evaluate the safety profile of Bevacizumab (Bevacizumab™)- Rituximab (Rituxan®)-CHOP (RA-CHOP) in patients with newly diagnosed mantle cell lymphoma (MCL).

Secondary Objectives

1. To evaluate the response rate and time to disease progression of the RA-CHOP regimen in patients with newly diagnosed MCL.

2. To prospectively characterize the angiogenic profiles of MCL patients during RA-CHOP treatment.

Condition or Disease	Intervention/Treatment	Phase
Untreated Mantle Cell Lymphoma	Drug: Bevacizumab; Drug: Rituximab; Drug: CHOP	Phase 2

Detailed Description

Bevacizumab administered at 15 mg/kg on day 1 of each of 6 cycles

Rituximab administered 375 mg/m2 on day 3 of each of 6 cycles (with usual premedications)

Standard CHOP chemotherapy administered on day 3 every 21 days (full dose) for 6 cycles of treatment

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: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Bevacizumab Plus CHOP-Rituximab in Patients With Untreated Mantle Cell Lymphoma (NHL)
• Actual Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Study Treatment Arm Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles

Drug: Bevacizumab; 15 mg/kg on day 1 of each of 6 cycles; Drug: Rituximab; Rituximab will be administered prior to CHOP on day 3 of every cycle for a total of 6 cycles. The dose to be administered is: Rituximab: 375 mg/m2; Drug: CHOP; Standard CHOP chemotherapy will be administered at full dose every 21 days for a total of 6 cycles. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 3 Doxorubicin: 50 mg/m2 IV on day 3 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 3 Prednisone: 100 mg PO days 3 - 7

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Toxicity [38 months]

   Number of patients with reversible myelosuppression (Primary toxicity was reversible myelosuppression) Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

Secondary Outcome Measures

1. Overall Response Rate [38 Months (min 33 months, max 62 months)]

   Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999)

2. Progression-Free Survival [3 years]

   The percentage of patients who have not progressed at the three year time point. The 3-year PFS rate was estimated based on the Kaplan-Meier analysis.

3. Overall Survival [3 years]

   The percentage of patients who have survived at the three year time point. The 3-year OS rate was estimated based on the Kaplan-Meier analysis.

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 mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-)

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

• Laboratory parameters (unless considered by investigator to be due to lymphoma):

Absolute neutrophil count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Hemoglobin > 7 gm/dL Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN

• Patient has at least one tumor mass > 1.5 cm in one dimension

• Available tumor tissue for correlative studies (rebiopsy to be performed if needed)

• Patient is > 18 years old

• Patient has KPS > 50%

• Patient has signed IRB-approved informed consent

• Patient agrees to use birth control for duration of study

Exclusion Criteria:

• Known central nervous system (CNS) involvement by lymphoma

• Known hepatitis infection

• Known HIV positivity

• Known history of renal disease with proteinuria; urine protein:creatinine ratio ³1.0 at screening

• Uncontrolled hypertension: blood pressure of >150/100 mmHg at screening

• Unstable angina

• History of myocardial infarction within 6 months

• History of stroke within 6 months

• Clinically significant peripheral vascular disease

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• Patient has ejection fraction < 50%

• Patient is taking coumadin, or has known history of thrombosis within last 6 months

• Evidence of bleeding diathesis or coagulopathy

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1

• Serious, non-healing wound, ulcer, or bone fracture

• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

• Patient is pregnant or nursing

• Patient is receiving other investigational drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612
2	Weill Medical College of Cornell University	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University

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: NCT00401817
• Other Study ID Numbers: 0604008463
• First Posted: Nov 22, 2006
• Last Update Posted: Oct 20, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Bevacizumab; Rituximab

Study Results

Participant Flow

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
Overall Participants	11
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	3 27.3%
Male	8 72.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Toxicity
Description	Number of patients with reversible myelosuppression (Primary toxicity was reversible myelosuppression) Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
Measure Participants	11
Number [participants]	8 72.7%

2. Secondary Outcome

Title	Overall Response Rate
Description	Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999)
Time Frame	38 Months (min 33 months, max 62 months)

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
Measure Participants	11
Number (95% Confidence Interval) [percentage of participants]	82 745.5%

3. Secondary Outcome

Title	Progression-Free Survival
Description	The percentage of patients who have not progressed at the three year time point. The 3-year PFS rate was estimated based on the Kaplan-Meier analysis.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles Rituximab: Rituximab will be administered prior to CHOP on day 3 of every cycle for a total of 6 cycles. The dose to be administered is: Rituximab: 375 mg/m2 CHOP: Standard CHOP chemotherapy will be administered at full dose every 21 days for a total of 6 cycles. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 3 Doxorubicin: 50 mg/m2 IV on day 3 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 3 Prednisone: 100 mg PO days 3 - 7
Measure Participants	11
Number (95% Confidence Interval) [percentage of patients]	23

4. Secondary Outcome

Title	Overall Survival
Description	The percentage of patients who have survived at the three year time point. The 3-year OS rate was estimated based on the Kaplan-Meier analysis.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Evaluable Patients

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
Measure Participants	11
Number (95% Confidence Interval) [percentage of patients]	82

Adverse Events

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles
All Cause Mortality
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)
Reproductive system and breast disorders
Prostate Cancer	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Neutropenia	3/11 (27.3%)
Anemia	8/11 (72.7%)
Thrombocytopenia	5/11 (45.5%)
Hypocalcemia	4/11 (36.4%)
Hyperkalemia	2/11 (18.2%)
Hypoalbuminemia	2/11 (18.2%)
Cardiac disorders
Left ventricular systolic dysfunction	2/11 (18.2%)
Hypertension	1/11 (9.1%)
Congestive heart failure	1/11 (9.1%)
General disorders
Bleeding	1/11 (9.1%)
Fatigue	7/11 (63.6%)
Constipation	3/11 (27.3%)
Edema	3/11 (27.3%)
Nausea	2/11 (18.2%)
Second malignancy	2/11 (18.2%)
Mouth sore	2/11 (18.2%)
Dyspnea	1/11 (9.1%)
Infections and infestations
Febrile Neutropenia	1/11 (9.1%)
Infection (normal ANC)	1/11 (9.1%)
Rituximab infusion rxn	4/11 (36.4%)
Metabolism and nutrition disorders
Anorexia	1/11 (9.1%)
Nervous system disorders
Neuropathy	4/11 (36.4%)
Renal and urinary disorders
Proteinuria	1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/11 (18.2%)

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.