Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms

• Sponsor: Eastern Cooperative Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00217425
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 110
• Arm: 1
• Duration (Months): 92
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with several chemotherapy drugs (combination chemotherapy) works in treating patients with peripheral T-cell lymphoma or natural killer cell neoplasms.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bevacizumab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: prednisone; Drug: vincristine	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the 12-month progression-free survival of patients with peripheral T-cell or natural killer cell neoplasms treated with bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP).

Secondary

• Determine the overall response rate (complete remission [CR, unconfirmed CR, or functional CR] and partial remission) in these patients after courses 3, 6, and 8 of this treatment regimen.

• Determine the overall survival of patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive 6-8 cycles of A-CHOP followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.

After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study within 22 months.

ACTUAL ACCRUAL: 46

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bevacizumab and CHOP (A-CHOP) in Combination for Patients With Peripheral T-Cell or Natural Killer Cell Neoplasms
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (A-CHOP followed by MA) Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.

Biological: bevacizumab; A - CHOP: 15 mg/kg IV infusion once every 21 days for 6-8 cycles. Bevacizumab is to be administered prior to CHOP therapy. Continuous bevacizumab: 15 mg/kg IV infusion once every 21 days. Initial dose should be infused over 90 minutes. If no adverse reactions occur, the second dose should be administered over 60 minutes. Again, if no adverse reactions occur, the third and subsequent doses should be administered over 30 minutes. If infusion-related adverse reactions occur, subsequent infusions should be administered over the shortest period that is well-tolerated. Infusions should be run in via a volumetric infusion device. Do NOT administer as an IV push or bolus.; Other Names: NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody. ; Drug: cyclophosphamide; IV infusion per institutional guidelines.; Other Names: Cytoxan, Neosar, CTX, CPM. ; Drug: doxorubicin; Intravenously, either as a bolus injection or as a continuous infusion through a central venous line.; Other Names: Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS, hydroxydaunorubicin, hydroxydaunomycin, ADR. ; Drug: prednisone; Prednisone is taken orally.; Other Names: Deltasone, Orasone, Medicorten, Panasol-S, Liquid-Pred. ; Drug: vincristine; IV push using extravasation precautions.; Other Names: Oncovin, Vincasar PFS vincristine sulfate, VCR, leucocristine, LCR.

Outcome Measures

Primary Outcome Measures

1. 12-Month Progression-Free Survival (PFS) [Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.]

   12-month progression-free survival is defined as the probability of patients remaining alive and progression-free at 12 months from study entry.

Secondary Outcome Measures

1. Overall Response Rate [Assessed after cycle 3, cycle 6, and cycle 8 (if given).]

   Overall response rate is defined as proportion of patients who achieve complete remission [CR, unconfirmed CR (CRu) or Functional CR] or partial remission. Response is assessed using the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Chesen, 1999).

2. 3-Year Overall Survival [Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.]

   3-year overall survival is defined as the probability of patients surviving at 3 years from study entry.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

• Diagnosis of peripheral T-cell or natural killer cell neoplasm

• Any stage disease allowed

• HTLV-positive tumors allowed

• At least one objective measurable disease parameter. Abnormal positron emission tomography scans are not considered evidence of measurable disease unless results are confirmed by CT scan or other appropriate imaging techniques

• Age 18 and over

• ECOG Performance status 0-2

• Absolute neutrophil count ≥ 1,000/mm^3(500/mm3 if due to bone marrow involvement with lymphoma)

• Platelet count ≥ 100,000/mm^3(50,000/mm3 if due to bone marrow involvement with lymphoma)

• Bilirubin ≤ 2.0 mg/dL (≤ 3 times upper limit of normal [ULN] if due to hepatic involvement with lymphoma)

• AST ≤ 2 times ULN (5 times ULN if due to hepatic involvement with lymphoma)

• PT, INR, and PTT ≤ 1.5 times normal

• Creatinine ≤ 2.0 mg/dL

• Urinary protein:creatinine ratio ≤ 1

• History of deep venous thrombosis allowed provided patient is on a stable dose of anticoagulants for at least 2 weeks prior to study entry

• LVEF ≥ 50%

• History of pulmonary embolism allowed provided patient is on a stable dose of anticoagulants for at least 2 weeks prior to study entry

• One prior cycle of CHOP for PTCL allowed

• More than 4 weeks since prior major invasive surgery or open biopsy

• At least 7 days since prior minor surgery. Peripheral lymph node core biopsy, bone marrow biopsy, fine needle aspiration, skin biopsy, or central line placement are not considered minor surgical procedures

• More than 7 days since prior and no concurrent anti-platelet drugs (e.g., ticlopidine, clopidogrel, or cilostazol) except aspirin or other nonsteroidal anti-inflammatory drugs

• Concurrent anticoagulants allowed provided patient is on a stable dose

• INR must be stable for at least 2 weeks prior to study entry

• PT/INR and/or PTT must be closely monitored and levels kept within acceptable range for underlying thrombotic disease

• Concurrent heparin flush for maintenance of central line patency allowed

EXCLUSION CRITERIA:

• Anaplastic lymphoma kinase (ALK)-positive T-cell large cell lymphoma. ALK-negative T-cell large cell lymphoma allowed

• Cutaneous T-cell lymphoma

• History of or current radiographic evidence of CNS metastasis, including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement

• Evidence of bleeding diathesis or coagulopathy

• Cerebrovascular accident within the past 6 months

• Myocardial infarction within the past 6 months

• Unstable angina within the past 6 months

• New York Heart Association class II-IV congestive heart failure

• Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg)

• Other clinically significant cardiovascular or peripheral vascular disease

• Abdominal fistula within the past 6 months

• Gastrointestinal perforation within the past 6 months

• Intra-abdominal abscess within the past 6 months

• Concurrent major surgery

• Pregnant or nursing. Female patients must have negative pregnancy test. Fertile patients must use effective contraception

• History of active seizures

• Significant traumatic injury within the past 4 weeks

• Non-healing ulcer (unless involved with lymphoma)

• Bone fracture

• Active infection requiring parenteral antibiotics

• HIV positivity

• Other active malignancy within the past 6 months except carcinoma in situ of the cervix or basal cell carcinoma of the skin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Cancer Care, Incorporated - Greenbrae	Greenbrae	California	United States	94904
2	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
3	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
4	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
5	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
6	Graham Hospital	Canton	Illinois	United States	61520
7	Memorial Hospital	Carthage	Illinois	United States	62321
8	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
9	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
10	Eureka Community Hospital	Eureka	Illinois	United States	61530
11	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
12	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
13	Mason District Hospital	Havana	Illinois	United States	62644
14	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
15	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
16	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
17	McDonough District Hospital	Macomb	Illinois	United States	61455
18	La Grange Oncology Associates - Geneva	Naperville	Illinois	United States	60563
19	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
20	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
21	Community Cancer Center	Normal	Illinois	United States	61761
22	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
23	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
24	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
25	Proctor Hospital	Peoria	Illinois	United States	61614
26	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
27	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
28	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
29	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
30	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
31	Perry Memorial Hospital	Princeton	Illinois	United States	61356
32	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
33	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
34	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
35	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
36	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
37	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
38	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
39	McFarland Clinic, PC	Ames	Iowa	United States	50010
40	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
41	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
42	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
43	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
44	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
45	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
46	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
47	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
48	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
49	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
50	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
51	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
52	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
53	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
54	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
55	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
56	Southwest Medical Center	Liberal	Kansas	United States	67901
57	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
58	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
59	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
60	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
61	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
62	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
63	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
64	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
65	CCOP - Wichita	Wichita	Kansas	United States	67214
66	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
67	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
68	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland	United States	21204
69	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
70	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
71	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
72	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
73	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
74	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
75	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
76	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
77	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
78	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
79	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
80	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
81	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
82	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
83	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
84	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
85	United Hospital	Saint Paul	Minnesota	United States	55102
86	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
87	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
88	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
89	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York	United States	10466
90	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
91	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
92	St. Rita's Medical Center	Lima	Ohio	United States	45801
93	Doylestown Hospital Cancer Center	Doylestown	Pennsylvania	United States	18901
94	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
95	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania	United States	17043
96	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
97	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
98	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
99	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
100	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
101	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
102	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
103	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
104	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
105	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
106	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
107	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
108	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
109	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
110	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• Eastern Cooperative Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Kristen N. Ganjoo, MD, Veterans Affairs Medical Center - Palo Alto

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00217425
• Other Study ID Numbers: CDR0000441194; U10CA021115; E2404
• First Posted: Sep 22, 2005
• Last Update Posted: May 7, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Eastern Cooperative Oncology Group: anaplastic large cell lymphoma; stage I adult T-cell leukemia/lymphoma; stage II adult T-cell leukemia/lymphoma; stage III adult T-cell leukemia/lymphoma; stage IV adult T-cell leukemia/lymphoma; peripheral T-cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Neoplasms; Prednisone; Cyclophosphamide; Bevacizumab; Doxorubicin; Liposomal doxorubicin; Vincristine

Study Results

Participant Flow

Arm/Group Title	Treatment (A-CHOP Followed by MA)
Arm/Group Description	Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
Period Title: Overall Study
STARTED	46
Treated	44
Eligible and Treated	39
COMPLETED	9
NOT COMPLETED	37

Baseline Characteristics

Arm/Group Title	Treatment (A-CHOP Followed by MA)
Arm/Group Description	Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	11 28.2%
Male	28 71.8%

Outcome Measures

1. Primary Outcome

Title	12-Month Progression-Free Survival (PFS)
Description	12-month progression-free survival is defined as the probability of patients remaining alive and progression-free at 12 months from study entry.
Time Frame	Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment (A-CHOP Followed by MA)
Arm/Group Description	Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
Measure Participants	39
Number (95% Confidence Interval) [probability]	0.44

2. Secondary Outcome

Title	Overall Response Rate
Description	Overall response rate is defined as proportion of patients who achieve complete remission [CR, unconfirmed CR (CRu) or Functional CR] or partial remission. Response is assessed using the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Chesen, 1999).
Time Frame	Assessed after cycle 3, cycle 6, and cycle 8 (if given).

Outcome Measure Data

Analysis Population Description

Eligible and treated

Arm/Group Title	Treatment (A-CHOP Followed by MA)
Arm/Group Description	Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
Measure Participants	39
Number (95% Confidence Interval) [proportion]	0.90

3. Secondary Outcome

Title	3-Year Overall Survival
Description	3-year overall survival is defined as the probability of patients surviving at 3 years from study entry.
Time Frame	Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment (A-CHOP Followed by MA)
Arm/Group Description	Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 [max. 2 mg]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
Measure Participants	39
Number (95% Confidence Interval) [probability]	0.39

Adverse Events

Time Frame	Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
Arm/Group Title	Treatment (ACHOP Followed by MA)
Arm/Group Description	Adverse events in all treated patients regardless of eligibility.
All Cause Mortality
	Treatment (ACHOP Followed by MA)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (ACHOP Followed by MA)
	Affected / at Risk (%)	# Events
Total	34/44 (77.3%)
Blood and lymphatic system disorders
Anemia	3/44 (6.8%)
Febrile neutropenia	8/44 (18.2%)
Cardiac disorders
Ventricular arrhythmia	1/44 (2.3%)
Left ventricular systolic dysfunction	4/44 (9.1%)
Restrictive cardiomyopathy	1/44 (2.3%)
Gastrointestinal disorders
Colitis	1/44 (2.3%)
Constipation	1/44 (2.3%)
Diarrhea	1/44 (2.3%)
Mucositis oral	1/44 (2.3%)
Colonic perforation	1/44 (2.3%)
Intra-abdominal hemorrhage	1/44 (2.3%)
Esophageal pain	1/44 (2.3%)
General disorders
Fatigue	6/44 (13.6%)
Death NOS	1/44 (2.3%)
Infections and infestations
Infections and infestations - Other, spe	2/44 (4.5%)
Infections and infestations - Other, spe	1/44 (2.3%)
Lung infection	1/44 (2.3%)
Anorectal infection	1/44 (2.3%)
Urinary tract infection	1/44 (2.3%)
Investigations
White blood cell decreased	14/44 (31.8%)
Lymphocyte count decreased	12/44 (27.3%)
Neutrophil count decreased	23/44 (52.3%)
Platelet count decreased	5/44 (11.4%)
Weight loss	1/44 (2.3%)
Aspartate aminotransferase increased	1/44 (2.3%)
Blood bilirubin increased	1/44 (2.3%)
Investigations - Other, specify	1/44 (2.3%)
Metabolism and nutrition disorders
Dehydration	1/44 (2.3%)
Hyperglycemia	2/44 (4.5%)
Hypophosphatemia	2/44 (4.5%)
Hyponatremia	4/44 (9.1%)
Nervous system disorders
Peripheral sensory neuropathy	1/44 (2.3%)
Headache	1/44 (2.3%)
Reproductive system and breast disorders
Vaginal inflammation	1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/44 (2.3%)
Dyspnea	2/44 (4.5%)
Hypoxia	1/44 (2.3%)
Vascular disorders
Hypertension	4/44 (9.1%)
Hypotension	1/44 (2.3%)
Thromboembolic event	3/44 (6.8%)
Other (Not Including Serious) Adverse Events
	Treatment (ACHOP Followed by MA)
	Affected / at Risk (%)	# Events
Total	39/44 (88.6%)
Blood and lymphatic system disorders
Anemia	15/44 (34.1%)
Eye disorders
Watering eyes	3/44 (6.8%)
Gastrointestinal disorders
Constipation	14/44 (31.8%)
Diarrhea	9/44 (20.5%)
Abdominal distension	4/44 (9.1%)
Gastritis	4/44 (9.1%)
Dyspepsia	9/44 (20.5%)
Mucositis oral	13/44 (29.5%)
Mucositis oral	5/44 (11.4%)
Nausea	15/44 (34.1%)
Vomiting	8/44 (18.2%)
Abdominal pain	4/44 (9.1%)
General disorders
Fatigue	29/44 (65.9%)
Fever	4/44 (9.1%)
Edema limbs	4/44 (9.1%)
Investigations
White blood cell decreased	7/44 (15.9%)
Lymphocyte count decreased	8/44 (18.2%)
Neutrophil count decreased	6/44 (13.6%)
Platelet count decreased	7/44 (15.9%)
Weight loss	12/44 (27.3%)
Alkaline phosphatase increased	6/44 (13.6%)
Alanine aminotransferase increased	3/44 (6.8%)
Aspartate aminotransferase increased	4/44 (9.1%)
Investigations - Other, specify	3/44 (6.8%)
Metabolism and nutrition disorders
Anorexia	12/44 (27.3%)
Hypoalbuminemia	4/44 (9.1%)
Hypocalcemia	3/44 (6.8%)
Hyperglycemia	19/44 (43.2%)
Hypokalemia	6/44 (13.6%)
Hyponatremia	7/44 (15.9%)
Musculoskeletal and connective tissue disorders
Back pain	3/44 (6.8%)
Myalgia	6/44 (13.6%)
Nervous system disorders
Dysgeusia	6/44 (13.6%)
Dizziness	3/44 (6.8%)
Peripheral sensory neuropathy	24/44 (54.5%)
Headache	5/44 (11.4%)
Psychiatric disorders
Insomnia	6/44 (13.6%)
Renal and urinary disorders
Proteinuria	6/44 (13.6%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/44 (9.1%)
Epistaxis	4/44 (9.1%)
Bronchopulmonary hemorrhage	6/44 (13.6%)
Pharyngolaryngeal pain	3/44 (6.8%)
Cough	3/44 (6.8%)
Dyspnea	7/44 (15.9%)
Voice alteration	3/44 (6.8%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/44 (6.8%)
Dry skin	5/44 (11.4%)
Alopecia	17/44 (38.6%)
Nail loss	4/44 (9.1%)
Rash maculo-papular	4/44 (9.1%)
Vascular disorders
Hypertension	5/44 (11.4%)

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.