Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma
Study Details
Study Description
Brief Summary
This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma. Monoclonal antibodies, such as rituximab, 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells.
Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C), vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the complete response (CR) rate in patients with mantle cell lymphoma, who are treated with VcR-CVAD.
SECONDARY OBJECTIVES:
-
To evaluate the overall response rate to VcR-CVAD. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients receiving maintenance rituximab after VcR-CVAD induction.
-
To evaluate the PFS and OS of patients who receive autologous stem cell transplantation (ASCT) after VcR-CVAD induction.
-
To evaluate the toxicity of VcR-CVAD.
TERTIARY OBJECTIVES:
-
Evaluation of antigen expression patterns to determine or confirm possible unique expressions of MCL.
-
To evaluate the percentage of circulating mantle cell lymphoma (MCL) cells.
OUTLINE: This is a multicenter study.
Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib 1.3 mg/m2 IV over 3-5 seconds on days 1 and 4; rituximab 375 mg/m2 IV over 3-4 hours on day 1; doxorubicin hydrochloride 25 mg/m2/d IV over 48 hours on days 1 and 2; cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours on days 1-3; vincristine 1 mg IV over 3-5 seconds on day 3; and dexamethasone 40 mg IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Maintenance therapy: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (ASCT) (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy.
After completion of study treatment, patients are followed periodically for up to 10 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VcR-CVAD induction followed by maintenance rituximab VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. |
Drug: bortezomib
Given IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: vincristine
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Biological: filgrastim
Given SC
Other Names:
Biological: pegfilgrastim
Given SC
Other Names:
|
| Experimental: VcR-CVAD induction followed by ASCT VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ASCT: After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy. |
Drug: bortezomib
Given IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: vincristine
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Biological: filgrastim
Given SC
Other Names:
Biological: pegfilgrastim
Given SC
Other Names:
Procedure: Autologous stem cell transplantation (ASCT)
|
Outcome Measures
Primary Outcome Measures
- Complete Response (CR) Rate [Assessed after VcR-CVAD cycles 2, 4, and 6.]
Number of eligible, treated participants who achieve complete response. Response criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
Secondary Outcome Measures
- 2-year Progression-free Survival (PFS) [Assessed every 6 months for 5 years, and then yearly thereafter.]
PFS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
- 3-year Overall Survival (OS) [Assessed every 6 months for 5 years, and then yearly thereafter.]
OS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to death. Patients alive at last follow-up were censored.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have a histologically confirmed diagnosis of mantle cell lymphoma by demonstrating appropriate morphology plus at least one of the following on the biopsy specimen: nuclear cyclin D1+ by immunohistochemistry; t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping
-
No prior chemotherapy, immunotherapy or radiotherapy for mantle cell lymphoma; a brief course of steroids (< 14 days) for symptom relief or steroids for other indications are allowed
-
Patients must have measurable disease; CT scans at baseline are required to define the extent of measurable disease; the scans must be obtained within 6 weeks prior to registration; combined CT/PET scans may be used for the baseline and subsequent evaluations if accurate tumor measurements can be obtained from the CT component
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-
Absolute neutrophil count (ANC) > 1500 mm^3 (unless low count due to marrow involvement or splenomegaly)
-
Platelets > 100,000 mm^3 (unless low counts due to marrow involvement or splenomegaly)
-
Creatinine < 2 mg/dL
-
Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to Gilbert's disease or due to liver involvement by lymphoma)
-
Patients over the age of 45 must have a left ventricular ejection fraction (LVEF) of greater than 45% documented within 90 days prior to registration
-
Patients must be tested for Hepatitis B surface antigen (HBs Ag) within 4 weeks prior to registration NOTE: HBs Ag positive patients are not excluded but will have more stringent monitoring of liver function tests
Exclusion Criteria:
-
Known HIV disease; an HIV test is not required for entry on study but is required if the patient is perceived to be at risk; patients with a history of intravenous drug use or any other behavior with an increased risk for HIV infection should be tested for exposure to the HIV virus; patients with known HIV are excluded since the immunocompromised state of patients with HIV infection or the concomitant use of highly active antiretroviral therapy (HAART) may result in more extensive dose modifications than intended for the intensive therapeutic regimen used in this study
-
Pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; women of childbearing potential and sexually active males must use an accepted and effective method of contraception
-
Grade 2 or higher baseline peripheral neuropathy
-
Known hypersensitivity to boron or mannitol
-
History of prior malignancy unless at least one of the following conditions are met:
-
Malignancy was in-situ
-
Malignancy was treated surgically or with local radiation therapy with curative intent and the patient has been disease free for > 3 years
-
Any adjuvant hormonal therapy must have been discontinued > 3 months prior to registration
-
Known central nervous system (CNS) involvement
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eastern Cooperative Oncology Group | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Study Chair: Brad Kahl, Eastern Cooperative Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02966
- NCI-2012-02966
- E1405
- E1405
- E1405
- U10CA021115
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | VcR-CVAD Induction Followed by Maintenance Rituximab | VcR-CVAD Induction Followed by ASCT | VcR-CVAD Induction Then Off Study |
|---|---|---|---|
| Arm/Group Description | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneous (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ASCT: After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy. | Patients received VcR-CVAD induction but did not proceed to step 2 treatment for various reasons. |
| Period Title: Step 1 - VcR-CVAD Induction | |||
| STARTED | 45 | 22 | 10 |
| Eligible and Treated | 44 | 22 | 9 |
| COMPLETED | 44 | 22 | 1 |
| NOT COMPLETED | 1 | 0 | 9 |
| Period Title: Step 1 - VcR-CVAD Induction | |||
| STARTED | 45 | 22 | 0 |
| Eligible and Treated | 44 | 22 | 0 |
| COMPLETED | 29 | 22 | 0 |
| NOT COMPLETED | 16 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Step 1 - VcR-CVAD Induction |
|---|---|
| Arm/Group Description | All eligible patients who received VcR-CVAD induction. |
| Overall Participants | 75 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
62
|
| Sex: Female, Male (Count of Participants) | |
| Female |
17
22.7%
|
| Male |
58
77.3%
|
Outcome Measures
| Title | Complete Response (CR) Rate |
|---|---|
| Description | Number of eligible, treated participants who achieve complete response. Response criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy. |
| Time Frame | Assessed after VcR-CVAD cycles 2, 4, and 6. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eligible and treated patients |
| Arm/Group Title | VcR-CVAD Induction |
|---|---|
| Arm/Group Description | All eligible patients who received VcR-CVAD induction. |
| Measure Participants | 75 |
| Number (95% Confidence Interval) [proportion] |
0.68
|
| Title | 2-year Progression-free Survival (PFS) |
|---|---|
| Description | PFS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored. |
| Time Frame | Assessed every 6 months for 5 years, and then yearly thereafter. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eligible and treated patients who received maintenance rituximab or ASCT |
| Arm/Group Title | VcR-CVAD Induction Followed by Maintenance Rituximab | VcR-CVAD Induction Followed by ASCT |
|---|---|---|
| Arm/Group Description | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ASCT: After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy. |
| Measure Participants | 44 | 22 |
| Number (95% Confidence Interval) [probability] |
0.79
|
0.76
|
| Title | 3-year Overall Survival (OS) |
|---|---|
| Description | OS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to death. Patients alive at last follow-up were censored. |
| Time Frame | Assessed every 6 months for 5 years, and then yearly thereafter. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eligible and treated patients who received maintenance rituximab or ASCT |
| Arm/Group Title | VcR-CVAD Induction Followed by Maintenance Rituximab | VcR-CVAD Induction Followed by ASCT |
|---|---|---|
| Arm/Group Description | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. | VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ASCT: After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy. |
| Measure Participants | 44 | 22 |
| Number (95% Confidence Interval) [probability] |
0.91
|
0.96
|
Adverse Events
| Time Frame | Assessed every 3 weeks while on treatment and for 30 days after the end of treatment | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Autologous stem cell transplantation (ASCT) was optional for this study, and submission of data with details on conditioning regimen or toxicity was not mandated. Therefore, the adverse event table for ASCT arm was not available. | |||
| Arm/Group Title | Step 1 - VcR-CVAD Induction | Step 2 - Maintenance Rituximab | ||
| Arm/Group Description | All patients who received VcR-CVAD induction. | All patients who received maintenance rituximab. | ||
All Cause Mortality |
||||
| Step 1 - VcR-CVAD Induction | Step 2 - Maintenance Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Step 1 - VcR-CVAD Induction | Step 2 - Maintenance Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 72/77 (93.5%) | 16/45 (35.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 22/77 (28.6%) | 1/45 (2.2%) | ||
| Hematologic-other | 1/77 (1.3%) | 0/45 (0%) | ||
| Febrile neutropenia | 9/77 (11.7%) | 0/45 (0%) | ||
| Eye disorders | ||||
| Keratitis | 1/77 (1.3%) | 0/45 (0%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 1/77 (1.3%) | 0/45 (0%) | ||
| Diarrhea w/o prior colostomy | 1/77 (1.3%) | 0/45 (0%) | ||
| Muco/stomatitis by exam, oral cavity | 1/77 (1.3%) | 0/45 (0%) | ||
| Nausea | 1/77 (1.3%) | 0/45 (0%) | ||
| Typhlitis | 1/77 (1.3%) | 0/45 (0%) | ||
| Vomiting | 1/77 (1.3%) | 0/45 (0%) | ||
| Upper GI, hemorrhage NOS | 1/77 (1.3%) | 0/45 (0%) | ||
| Abdomen, pain | 1/77 (1.3%) | 0/45 (0%) | ||
| General disorders | ||||
| Fatigue | 8/77 (10.4%) | 1/45 (2.2%) | ||
| Immune system disorders | ||||
| Allergic reaction | 1/77 (1.3%) | 0/45 (0%) | ||
| Infections and infestations | ||||
| Infection w/ gr3-4 neut, catheter relate | 1/77 (1.3%) | 0/45 (0%) | ||
| Infection w/ gr3-4 neut, lung | 1/77 (1.3%) | 0/45 (0%) | ||
| Infection Gr0-2 neut, catheter | 1/77 (1.3%) | 0/45 (0%) | ||
| Infection Gr0-2 neut, heart | 0/77 (0%) | 0/45 (0%) | ||
| Infection Gr0-2 neut, lung | 2/77 (2.6%) | 1/45 (2.2%) | ||
| Infection Gr0-2 neut, skin | 1/77 (1.3%) | 0/45 (0%) | ||
| Infection w/ gr3-4 neut, blood | 2/77 (2.6%) | 0/45 (0%) | ||
| Investigations | ||||
| Leukocytes decreased | 52/77 (67.5%) | 3/45 (6.7%) | ||
| Lymphopenia | 50/77 (64.9%) | 12/45 (26.7%) | ||
| Neutrophils decreased | 62/77 (80.5%) | 7/45 (15.6%) | ||
| Platelets decreased | 49/77 (63.6%) | 0/45 (0%) | ||
| Weight gain | 0/77 (0%) | 1/45 (2.2%) | ||
| Alkaline phosphatase increased | 1/77 (1.3%) | 0/45 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 4/77 (5.2%) | 0/45 (0%) | ||
| Dehydration | 2/77 (2.6%) | 0/45 (0%) | ||
| Hypocalcemia | 1/77 (1.3%) | 0/45 (0%) | ||
| Hyperglycemia | 5/77 (6.5%) | 0/45 (0%) | ||
| Hypophosphatemia | 2/77 (2.6%) | 0/45 (0%) | ||
| Hypokalemia | 3/77 (3.9%) | 0/45 (0%) | ||
| Hyponatremia | 2/77 (2.6%) | 0/45 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 1/77 (1.3%) | 0/45 (0%) | ||
| Nonneuropathic generalized weakness | 1/77 (1.3%) | 0/45 (0%) | ||
| Back, pain | 1/77 (1.3%) | 0/45 (0%) | ||
| Nervous system disorders | ||||
| Syncope | 1/77 (1.3%) | 0/45 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 2/77 (2.6%) | 0/45 (0%) | ||
| Renal and urinary disorders | ||||
| Cystitis | 1/77 (1.3%) | 0/45 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Throat/pharynx/larynx, pain | 1/77 (1.3%) | 0/45 (0%) | ||
| Dyspnea | 1/77 (1.3%) | 0/45 (0%) | ||
| Pleural effusion (non-malignant) | 0/77 (0%) | 0/45 (0%) | ||
| Pneumonitis/pulmonary infiltrates | 0/77 (0%) | 0/45 (0%) | ||
| Vascular disorders | ||||
| Hypotension | 1/77 (1.3%) | 0/45 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Step 1 - VcR-CVAD Induction | Step 2 - Maintenance Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 76/77 (98.7%) | 40/45 (88.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 71/77 (92.2%) | 26/45 (57.8%) | ||
| Hematologic-other | 4/77 (5.2%) | 0/45 (0%) | ||
| Eye disorders | ||||
| Vision-blurred | 5/77 (6.5%) | 0/45 (0%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 41/77 (53.2%) | 3/45 (6.7%) | ||
| Diarrhea w/o prior colostomy | 21/77 (27.3%) | 0/45 (0%) | ||
| Dyspepsia | 10/77 (13%) | 0/45 (0%) | ||
| Muco/stomatitis by exam, oral cavity | 5/77 (6.5%) | 0/45 (0%) | ||
| Muco/stomatitis (symptom) oral cavity | 12/77 (15.6%) | 0/45 (0%) | ||
| Nausea | 53/77 (68.8%) | 0/45 (0%) | ||
| Vomiting | 23/77 (29.9%) | 0/45 (0%) | ||
| Abdomen, pain | 6/77 (7.8%) | 0/45 (0%) | ||
| General disorders | ||||
| Fatigue | 65/77 (84.4%) | 13/45 (28.9%) | ||
| Fever w/o neutropenia | 6/77 (7.8%) | 0/45 (0%) | ||
| Rigors/chills | 6/77 (7.8%) | 0/45 (0%) | ||
| Edema limb | 19/77 (24.7%) | 0/45 (0%) | ||
| Investigations | ||||
| Leukocytes decreased | 39/77 (50.6%) | 21/45 (46.7%) | ||
| Lymphopenia | 39/77 (50.6%) | 27/45 (60%) | ||
| Neutrophils decreased | 34/77 (44.2%) | 12/45 (26.7%) | ||
| Platelets decreased | 67/77 (87%) | 19/45 (42.2%) | ||
| Weight gain | 6/77 (7.8%) | 0/45 (0%) | ||
| Weight loss | 7/77 (9.1%) | 0/45 (0%) | ||
| Alkaline phosphatase increased | 6/77 (7.8%) | 0/45 (0%) | ||
| Alanine aminotransferase increased | 10/77 (13%) | 0/45 (0%) | ||
| Aspartate aminotransferase increased | 10/77 (13%) | 0/45 (0%) | ||
| Creatinine increased | 6/77 (7.8%) | 0/45 (0%) | ||
| Metabolic/Laboratory-other | 7/77 (9.1%) | 0/45 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 25/77 (32.5%) | 0/45 (0%) | ||
| Hypoalbuminemia | 8/77 (10.4%) | 0/45 (0%) | ||
| Hypocalcemia | 20/77 (26%) | 0/45 (0%) | ||
| Hyperglycemia | 26/77 (33.8%) | 4/45 (8.9%) | ||
| Hypomagnesemia | 5/77 (6.5%) | 0/45 (0%) | ||
| Hypophosphatemia | 6/77 (7.8%) | 0/45 (0%) | ||
| Hypokalemia | 11/77 (14.3%) | 3/45 (6.7%) | ||
| Hyponatremia | 13/77 (16.9%) | 0/45 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back, pain | 7/77 (9.1%) | 0/45 (0%) | ||
| Bone, pain | 10/77 (13%) | 0/45 (0%) | ||
| Joint, pain | 4/77 (5.2%) | 0/45 (0%) | ||
| Muscle, pain | 6/77 (7.8%) | 0/45 (0%) | ||
| Nervous system disorders | ||||
| Taste disturbance | 11/77 (14.3%) | 0/45 (0%) | ||
| Dizziness | 9/77 (11.7%) | 0/45 (0%) | ||
| Neuropathy-sensory | 28/77 (36.4%) | 10/45 (22.2%) | ||
| Head/headache | 7/77 (9.1%) | 0/45 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 19/77 (24.7%) | 0/45 (0%) | ||
| Depression | 4/77 (5.2%) | 0/45 (0%) | ||
| Renal and urinary disorders | ||||
| Urinary frequency/urgency | 4/77 (5.2%) | 0/45 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 12/77 (15.6%) | 0/45 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 0/77 (0%) | 3/45 (6.7%) | ||
| Alopecia | 28/77 (36.4%) | 6/45 (13.3%) | ||
| Nail changes | 4/77 (5.2%) | 0/45 (0%) | ||
| Rash/desquamation | 6/77 (7.8%) | 0/45 (0%) | ||
| Vascular disorders | ||||
| Hypotension | 5/77 (6.5%) | 0/45 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Study Statistician |
|---|---|
| Organization | ECOG Statistical Office |
| Phone | 617-632-3012 |
- NCI-2012-02966
- NCI-2012-02966
- E1405
- E1405
- E1405
- U10CA021115