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Phase 2 Study of VELCADE (Bortezomib) in Patients With Relapsed Follicular Lymphoma

Phase 2
Completed
Conditions
Relapsed Follicular Lymphoma
Interventions
Registration Number
NCT00715208
Lead Sponsor
Millennium Pharmaceuticals, Inc.
Brief Summary

This is a phase 2, two-arm, non-randomized, open-label, multicenter study evaluating the safety and efficacy of 2 VELCADE-containing regimens. Patients will be treated with either a combination of VELCADE, rituximab, cyclophosphamide, doxorubicin, and prednisone (VELCADE-R-CAP) or a combination of VELCADE, rituximab, cyclophosphamide, and prednisone (VELCADE-R-CP) based on investigator preference. Following completion of the treatment period, patients will receive maintenance therapy with rituximab up to a maximum of 2 years.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
55
Inclusion Criteria
  • Male or female patient 18 years of age or older
  • Pathological diagnosis of follicular lymphoma (any grade) or marginal zone lymphoma. Patients with transformed follicular lymphoma are eligible, provided there has previously been pathologic documentation of follicular lymphoma.
  • Documented relapse or progression following prior antineoplastic therapy
  • At least 1 measurable tumor mass that is greater than 1.5 cm in the long axis and greater than 1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation
  • No clinically significant evidence of active central nervous system lymphoma
  • Karnofsky performance status (KPS) ≥50 (equivalent to Eastern Cooperative Group Oncology Group [ECOG] status ≤2)
Exclusion Criteria
  • Diagnosed or treated for a malignancy other than Non-Hodgkin's Lymphoma (NHL) within 2 years of first dose, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Patients with prostate cancer who were treated with definitive radiotherapy who have a serum prostate-specific antigen <1 ng/mL are not excluded. Patients are not excluded if they have had basal cell or squamous cell carcinoma of the skin that was completely resected, or any in situ malignancy that was adequately treated.

  • Received any of the following treatments or procedures outside of the specified timeframes:

    • Prior treatment with VELCADE
    • Prior treatment with a cumulative dose of doxorubicin of more than 100 mg/m2, if assigned to Arm A (VELCADE-R-CAP)
    • Antineoplastic (including unconjugated therapeutic antibodies and toxin immunoconjugates), experimental, or radiation therapy within 3 weeks before Day 1 of Cycle 1
    • Nitrosoureas within 6 weeks before Day 1 of Cycle 1
    • Radioimmunoconjugates within 10 weeks before Day 1 of Cycle 1
    • Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time
    • Major surgery within 2 weeks before Day 1 of Cycle 1

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VELCADE R-CAPVELCADEVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CPVELCADEVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CAPrituximabVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CAPcyclophosphamideVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CAPdoxorubicinVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CAPprednisoneVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CPcyclophosphamideVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CPrituximabVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
VELCADE R-CPprednisoneVELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.
Primary Outcome Measures
NameTimeMethod
Number of Patients With Complete Response (CR)30 weeks

Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Overall Response (OR)30 weeks

OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria.

CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET.

Percentage of Participants With Progression-free Survival (PFS) at 1 YearAssessed at at the end of Cycle 2, at end of treatment visit, and every 12± 1 weeks for the first year (4 visits) until PD

PFS was defined as the time from the first dose to the date of progressive disease (PD)/relapse or death, whichever comes first. For a participant who had not progressed/relapsed or died, PFS was censored at the last response assessment that was stable disease (failure to attain complete response/partial response or PD or better).

Duration of Response2 years

Time (in months) from the first documentation of a response (CR or partial response \[PR\]) to the date of first documentation of progressive disease or relapse from complete response.

CR is defined as disappearance of all evidence of disease assessed by CT or PET; PR is defined as regression of measurable disease and no new sites assessed by CT or PET according to the revised International Working Group (IWG) Criteria.

Number of Patients Who Experienced at Least One Serious Adverse EventFrom completion of informed consent through 30 days after the last dose of study drug

Trial Locations

Locations (42)

Loma Linda U Cancer Center

🇺🇸

Loma Linda, California, United States

Oklahoma Oncology and Hematology, PC

🇺🇸

Tulsa, Oklahoma, United States

Desert Hematology Medical Group, Inc.

🇺🇸

Rancho Mirage, California, United States

Kalamazoo Hematology and Oncology

🇺🇸

Kalamazoo, Michigan, United States

Nebraska Hematology-Oncology, PC

🇺🇸

Lincoln, Nebraska, United States

Temple University

🇺🇸

Philadelphia, Pennsylvania, United States

Allegheny-Singer Research Institute

🇺🇸

Pittsburgh, Pennsylvania, United States

Western Pennsylvania Cancer Institute

🇺🇸

Pittsburgh, Pennsylvania, United States

New York Medical College

🇺🇸

Valhalla, New York, United States

University of Tennessee Medical Center

🇺🇸

Knoxville, Tennessee, United States

Marshall University

🇺🇸

Huntington, West Virginia, United States

Southern Nevada Cancer Research Foundation

🇺🇸

Las Vegas, Nevada, United States

Northwest Alabama Center, PC

🇺🇸

Muscle Shoals, Alabama, United States

Providence Saint Joseph Medical Center

🇺🇸

Burbank, California, United States

Pacific Coast Hematology Oncology Medical Group

🇺🇸

Fountain Valley, California, United States

Cancer Care Center, Inc.

🇺🇸

New Albany, Indiana, United States

Northwest Georgia Oncology Centers, PC

🇺🇸

Marietta, Georgia, United States

Alexian Brothers Hospital Network

🇺🇸

Elk Grove Village, Illinois, United States

Gabrail Cancer Center

🇺🇸

Canton, Ohio, United States

Cancer Center of Central Connecticut

🇺🇸

Southington, Connecticut, United States

Southern Illinois Hematology Oncology

🇺🇸

Centralia, Illinois, United States

Clintell, Inc.

🇺🇸

Skokie, Illinois, United States

Ocala Cancer Institute

🇺🇸

Ocala, Florida, United States

Siouxland Hematology Oncology Associates

🇺🇸

Sioux City, Iowa, United States

Hutchinson Clinic

🇺🇸

Hutchinson, Kansas, United States

Purchase Cancer Group

🇺🇸

Paducah, Kentucky, United States

Medical Oncology, LLC

🇺🇸

Baton Rouge, Louisiana, United States

Jackson Oncology Associates, PLLC

🇺🇸

Jackson, Mississippi, United States

St. Louis Cancer Care, LLP

🇺🇸

Chesterfield, Missouri, United States

Great Plains Regional Medical Center

🇺🇸

North Platte, Nebraska, United States

San Juan Oncology Associates

🇺🇸

Farmington, New Mexico, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Interlakes Foundation

🇺🇸

Rochester, New York, United States

NYU Clinical Cancer Center

🇺🇸

New York, New York, United States

Avera Cancer Institute

🇺🇸

Sioux Falls, South Dakota, United States

Landmark Medical Center

🇺🇸

Woonsocket, Rhode Island, United States

West Virginia University Health Science Center

🇺🇸

Morgantown, West Virginia, United States

HOPE Oncology

🇺🇸

Richardson, Texas, United States

Auxilio Cancer Center

🇵🇷

Hato Rey, Puerto Rico

Northern Utah Associates

🇺🇸

Ogden, Utah, United States

Marshfield Clinic

🇺🇸

Marshfield, Wisconsin, United States

St. Joseph Mercy Hospital

🇺🇸

Ann Arbor, Michigan, United States

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