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

Lymphoma Clinical Trial

Official title:

Bevacizumab and CHOP (A-CHOP) in Combination for Patients With Peripheral T-Cell or Natural Killer Cell Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00217425
• Other study ID #: CDR0000441194
• Secondary ID: U10CA021115E2404
• Status: Completed
• Phase: Phase 2
• Start date: September 14, 2006
• Est. completion date: March 2014

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: March 2014
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Neoplasms

Intervention

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.

Drug:
• cyclophosphamide
IV infusion per institutional guidelines.
• doxorubicin
Intravenously, either as a bolus injection or as a continuous infusion through a central venous line.
• prednisone
Prednisone is taken orally.
• vincristine
IV push using extravasation precautions.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12-Month Progression-Free Survival (PFS)	12-month progression-free survival is defined as the probability of patients remaining alive and progression-free at 12 months from study entry.	Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.
Secondary	Overall Response Rate	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).	Assessed after cycle 3, cycle 6, and cycle 8 (if given).
Secondary	3-Year Overall Survival	3-year overall survival is defined as the probability of patients surviving at 3 years from study entry.	Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.