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| ID | Type | Description | Link |
|---|---|---|---|
| U10CA032102 | U.S. NIH Grant/Contract | View source | |
| S0213 | Other Identifier | SWOG |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining rituximab with chemotherapy may kill more cancer cells.
PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with rituximab in treating patients who have newly diagnosed mantle cell lymphoma.
OBJECTIVES:
OUTLINE: This is a pilot, multicenter study.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for 3 years. Patients with disease progression are followed annually for up to 5 years from study entry.
PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hyper-CVAD + MTX/Ara-C + Rituximab | Experimental | 21-day cycles of Hyper-CVAD and high-dose methotrexate/cytarabine are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6. Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and filgrastim 5 ug/kg on days 8-21. Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological | 5 ug/kg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival | Progression-Free Survival (PFS) rate at 1 year. PFS measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is a 50% increase in the sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed if a complete response (confirmed, or unconfirmed) was not previously achieved; appearance of a new lesion/site; unequivocal progression of non-measurable disease; or death due to disease without prior documentation of progression. | assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration |
| Measure | Description | Time Frame |
|---|---|---|
| Response | Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of nodes; no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. CRU is complete disappearance of all measurable and non-measurable disease; regressed, non-palpable organs; and one or more exceptions not qualifying for CR (see protocol section 10). PR applies to patients with at least one measurable lesion who do not qualify for CR or CRU. PR is a 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. |
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DISEASE CHARACTERISTICS:
Histologically proven stage III/IV or bulky stage II mantle cell lymphoma of one of the following histologic subtypes:
Newly diagnosed and previously untreated disease
Bidimensionally measurable disease
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
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| Name | Affiliation | Role |
|---|---|---|
| Elliot M. Epner, MD, PhD | OHSU Knight Cancer Institute | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | A multi center trial of hyperCVAD+rituxan in patients with newly diagnosed mantle cell lymphoma EM Epner; J Unger; T Miller; L Rimsza; C Spier; M LeBlanc; R Fisher. Blood 110(11):#387. (2007). |
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| ID | Title | Description |
|---|---|---|
| FG000 | Hyper-CVAD + MTX/Ara-C + Rituximab | 21-day cycles of Hyper-CVAD and high-dose methotrexate/Ara-C are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6. Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and G-CSF 5 ug/kg on days 8-21. Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Hyper-CVAD + MTX/Ara-C + Rituximab | 21-day cycles of Hyper-CVAD and high-dose methotrexate/Ara-C are alternated beginning with Hyper-CVAD for a maximum of 8 cycles. Rituximab is given for cycles 1-6. Hyper-CVAD (cycles 1,3,5,7): rituximab 375 mg/m^2 on day 1, mesna 600 mg/m^2 on days 2-4, cyclophosphamide 300 mg/m^2 on days 2-4, doxorubicin 16.6 mg/m^2/day on days 5-7, vincristine 1.4 mg/m^2 on days 5 and 12, dexamethasone 40 mg on days 2-5 and 12-15, and G-CSF 5 ug/kg on days 8-21. Methotrexate/Ara-C (cycles 2,4,6,8): rituximab 375 mg/m^2 on day 1, methotrexate 1000 mg/m^2 over days 2-3, Ara-C 12 g/m^2 over days 3-4, leucovorin 170 mg over days 3-5, and G-CSF 5 ug/kg on days 5-21. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-free Survival | Progression-Free Survival (PFS) rate at 1 year. PFS measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is a 50% increase in the sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed if a complete response (confirmed, or unconfirmed) was not previously achieved; appearance of a new lesion/site; unequivocal progression of non-measurable disease; or death due to disease without prior documentation of progression. | Posted | Number | 95% Confidence Interval | percentage of participants | assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration |
|
Every week while on protocol treatment (through 8 cycles or 168 days), and 3 months after removal from protocol treatment (at between 8 and 9 months after beginning treatment).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hyper-CVAD + MTX/Ara-C + Rituximab |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (2.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Statistician | SWOG Statistical Center | 206-667-4623 |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D000069283 | Rituximab |
| D003520 | Cyclophosphamide |
| D003561 | Cytarabine |
| D003907 | Dexamethasone |
| D004317 | Doxorubicin |
| D002955 | Leucovorin |
| D008727 | Methotrexate |
| D014750 | Vincristine |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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| rituximab | Biological | 375 mg/m^2 on day 1 of cycles 1-6 |
|
| cyclophosphamide | Drug | 300 mg/m^2 on days 2-4 of cycles 1,3,5,7 |
|
|
| cytarabine | Drug | 12 g/m^2 over days 3-4 of cycles 2,4,6,8 |
|
|
| dexamethasone | Drug | 40 mg on days 2-5 and 12-15 of cycles 1,3,5,7 |
|
| doxorubicin | Drug | 16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7 |
|
|
| leucovorin | Drug | 170 mg over days 3-5 of cycles 2,4,6,8 |
|
|
| methotrexate | Drug | 1000 mg/m^2 over days 2-3 of cycles 2,4,6,8 |
|
|
| vincristine | Drug | 1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7 |
|
|
| assessed after cycle 4 and after completion of treatment (168 days) |
| Overall Survival | Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause. | assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years |
| Withdrawal by Subject |
|
| Physician Decision |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Response | Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of nodes; no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. CRU is complete disappearance of all measurable and non-measurable disease; regressed, non-palpable organs; and one or more exceptions not qualifying for CR (see protocol section 10). PR applies to patients with at least one measurable lesion who do not qualify for CR or CRU. PR is a 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. | Posted | Number | participants | assessed after cycle 4 and after completion of treatment (168 days) |
|
|
|
| Secondary | Overall Survival | Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause. | Posted | Number | 95% Confidence Interval | percentage of participants | assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years |
|
|
|
| 4 |
| 49 |
| 48 |
| 49 |
| Infection with 3-4 neutropenia | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| Second primary | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (2.0) | Systematic Assessment |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (2.0) | Systematic Assessment |
|
| PRBC transfusion | Blood and lymphatic system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Platelet transfusion | Blood and lymphatic system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (2.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (2.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE (2.0) | Systematic Assessment |
|
| Abdominal pain/cramping | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Constipation/bowel obstruction | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Diarrhea without colostomy | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Dyspepsia/heartburn | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Esophagitis/dysphagia | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Stomatitis/pharyngitis | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Edema | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Fatigue/malaise/lethargy | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Fever without neutropenia | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hemorrhage w/ 3-4 thrombocyt | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Pain-other | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Rigors/chills | General disorders | CTCAE (2.0) | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Infection w/o 3-4 neutropenia | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| Infection with 3-4 neutropenia | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| Respiratory infect w/ neutrop | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| Respiratory infect w/o neutrop | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| Alkaline phosphatase increase | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Bilirubin increase | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Creatinine increase | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Leukopenia | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Lymphopenia | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Neutropenia/granulocytopenia | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| SGOT (AST) increase | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| SGPT (ALT) increase | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Thrombocytopenia | Investigations | CTCAE (2.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hyperuricemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (2.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Muscle weakness (not neuro) | Musculoskeletal and connective tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Myalgia/arthralgia, NOS | Musculoskeletal and connective tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Dizziness/vertigo, NOS | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Sensory neuropathy | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Taste disturbance | Nervous system disorders | CTCAE (2.0) | Systematic Assessment |
|
| Anxiety/agitation | Psychiatric disorders | CTCAE (2.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (2.0) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (2.0) | Systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Pneumonitis/infiltrates | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Petechiae/purpura | Skin and subcutaneous tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (2.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (2.0) | Systematic Assessment |
|
| Phlebitis | Vascular disorders | CTCAE (2.0) | Systematic Assessment |
|
| Thrombosis/embolism | Vascular disorders | CTCAE (2.0) | Systematic Assessment |
|
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| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008228 | Lymphoma, Non-Hodgkin |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D000630 | Aminopterin |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D054836 | Indolizidines |
| D007212 | Indolizines |