A Randomized, Open-Label, Multicenter Phase 3 Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone (VcR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly Diagnosed Mantle Cell Lymphoma Who Are Not Eligible for a Bone Marrow Transplant
Overview
- Phase
- Phase 3
- Intervention
- Rituximab 375 mg/m^2
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Enrollment
- 487
- Locations
- 150
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a randomized, open-label, multicenter, prospective study to compare the efficacy and safety of the combination of VcR-CAP to that of R-CHOP in participants who have newly diagnosed mantle cell lymphoma grade II, III or IV and who are ineligible to undergo bone marrow transplantation.
Detailed Description
The drug being tested in this study were combination of VcR-CAP and R-CHOP. Combination of VcR-CAP and R-CHOP is being tested to treat people who had mantle cell lymphoma (MCL). The study enrolled 487 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in a 1:1 ratio: Treatment Group A (VcR-CAP) Treatment Group B (R-CHOP) The study included a screening phase, a treatment phase, a short-term follow-up phase, and a long-term follow-up phase. The screening phase was up to 28 days (56 days for bone marrow evaluation) prior to randomization. This multi-center trial was conducted worldwide. The total study duration from randomization of the first patient until the last progression-free survival (PFS) event required for the final analysis was expected to be approximately 42 months (24 months for enrollment and 18 months for follow-up) and survival follow-up every 12 weeks until death.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients 18 years or older (the patient must be at least the legal age limit to be able to give informed consent within the jurisdiction the study is taking place)
- •Diagnosis of mantle cell lymphoma MCL (Stage II, III or IV) as evidenced by lymph node histology and either expression of cyclin D1 (in association with CD20 and CD5) or evidence of t(11;14) translocation, such as by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR). Patients with a diagnosis of Stage I MCL will not be permitted to enter study.
- •Paraffin embedded biopsy tissue block (preferably of lymph node origin) must be sent to the central laboratory for confirmation of MCL diagnosis prior to randomization. In China, a paraffin embedded lymph node biopsy tissue block must be sent for central confirmation of sample adequacy, prior to randomization
- •At least 1 measurable site of disease
- •No prior therapies for MCL
- •Not eligible for bone marrow transplantation as assessed by the treating physician (e.g., age or the presence of co-morbid conditions that may have a negative impact on the tolerability to transplantation).
- •Eastern Cooperative Oncology Group ECOG status ≤2
- •Absolute neutrophil count (ANC) ≥1500 cells/µL,
- •Platelets ≥100,000 cells/µL or ≥75,000 cells/µL if thrombocytopenia is considered by the investigator to be secondary to MCL (e.g., due to bone marrow infiltration or sequestration from splenomegaly).
- •Alanine transaminase ≤3 x upper limit of normal (ULN)
Exclusion Criteria
- •Prior treatment with VELCADE
- •Prior antineoplastic (including unconjugated therapeutic antibodies), experimental or radiation therapy, radioimmunoconjugates or toxin immunoconjugates for the treatment of MCL. In the event that a patient has received doxorubicin for the treatment of any condition, other than MCL, the maximum dose and exposure received prior to entry into this study should not exceed 150 mg/m
- •short course (maximum of 10 days, not exceeding 100 mg/day) prednisone or equivalent steroids are allowed to treat symptoms in patients with advanced disease who enter the screening phase and are waiting to be randomized.
- •Major surgery (at the discretion of the treating physician and in consultation with the sponsor's medical monitor) within 2 weeks before randomization
- •Peripheral neuropathy or neuropathic pain of Grade 2 or worse (as per the investigators assessment)
- •Diagnosed or treated for a malignancy other than MCL within 1 year of randomization, or who were previously diagnosed with a malignancy other than MCL and have any radiographic or biochemical marker evidence of malignancy. Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
- •Active systemic infection requiring treatment and patients with known diagnosis of human immunodeficiency virus HIV or active hepatitis B (carriers of hepatitis B are permitted to enter study)
- •History of allergic reaction attributable to compounds containing boron, mannitol, or hydroxybenzoates
- •Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate
- •Female or male patients of child-bearing potential who will not use adequate contraception during the course of the study.
Arms & Interventions
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Rituximab 375 mg/m^2
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Cyclophosphamide 750 mg/m^2
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Doxorubicin 50 mg/m^2
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Prednisone 100 mg/m^2
R-CHOP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, Vincristine 1.4 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Vincristine 1.4 mg/m^2
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Rituximab 375 mg/m^2
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Cyclophosphamide 750 mg/m^2
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Doxorubicin 50 mg/m^2
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: VELCADE 1.3 mg/m^2
VcR-CAP
Rituximab 375 mg/m\^2, Cyclophosphamide 750 mg/m\^2, Doxorubicin 50 mg/m\^2, VELCADE 1.3 mg/m\^2, and Prednisone 100 mg/m\^2
Intervention: Prednisone 100 mg/m^2
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Median duration of follow-up of 40 months
PFS was defined as the interval between the date of randomization and the date of progressive disease (PD) or death, whichever occurred first. PD was based on the assessment of an Independent Review Committee.
Secondary Outcomes
- Time to Progression (TTP)(Median duration of follow-up of 40 months)
- Overall Complete Response (CR + CRu)(Median duration of follow-up of 40 months)
- Duration of Response(Median duration of follow-up of 40 months)
- Time to Next Anti-lymphoma Treatment (TTNT)(: Median duration of follow-up of 40 months)
- Treatment-free Interval (TFI)(Median duration of follow-up of 40 months)
- Overall Response Rate (ORR)(Median duration of follow-up of 40 months)
- Overall Survival (OS)(Median duration of follow-up of 40 months)
- Number of Participants Experiencing an Adverse Event (AE)(Up to 107.4 months)
- 18-Month Survival(Up to month 18 from the time of randomization)
- Overall Survival (OS) in Long Term Follow-up Period(Up to 107.4 months)