Clinical trial NCT00217425: Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms
Official title: Bevacizumab and CHOP (A-CHOP) in Combination for Patients With Peripheral T-Cell or Natural Killer Cell Neoplasms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-22
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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/mm\^3 if due to bone marrow involvement with lymphoma)
* Platelet count ≥ 100,000/mm\^3(50,000/mm\^3 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

Primary outcomes:
measure: 12-Month Progression-Free Survival (PFS)
timeFrame: Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Assessed after cycle 3, cycle 6, and cycle 8 (if given).
measure: 3-Year Overall Survival
timeFrame: Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: California Cancer Care, Incorporated - Greenbrae
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Midwest Center for Hematology/Oncology
state: Illinois
city: Libertyville
country: United States
facility: North Shore Oncology and Hematology Associates, Limited - Libertyville
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Naperville
country: United States
facility: La Grange Oncology Associates - Geneva
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland - Niles
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates - Skokie
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Doylestown
country: United States
facility: Doylestown Hospital Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lemoyne
country: United States
facility: Central Pennsylvania Hematology and Medical Oncology Associates, PC
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Veterans Affairs Medical Center - Palo Alto
name: Kristen N. Ganjoo, MD
role: STUDY_CHAIR
References: