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| ID | Type | Description | Link |
|---|---|---|---|
| SCCC-2003027 | Other Identifier | University of Miami Sylvester Comprehensive Cancer Center | |
| WIRB-20051242 | Other Identifier | Western Institutional Review Board |
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RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with thalidomide maintenance in patients with newly diagnosed mantle cell lymphoma
PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: During cycle 1, patients will receive rituximab intravenous (IV), granisetron IV, decadron IV, doxorubicin IV bolus, vincristine intravenous pyelogram (IVP) on day 1; cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV, methotrexate by continuous infusion, then leucovorin IV until methotrexate level is below 0.01 nanomolar (nM) on day 10. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover.
When absolute neutrophil count (ANC) reaches1,500/mm^3, patients will start cycle 2. Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV, mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing until ANC is greater than 1,000 cells/mm^3.
Approximately 2-3 weeks later, patients receive another course of therapy as above.After cycle 4, patients in complete remission will take oral thalidomide until progression of disease. After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter or at study termination.
PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| R-MACLO-IVAM-T | Experimental | Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Drug | Rituximab 375 mg/m2 IV, Days 1 of all cycles |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival Rate | Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion. | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival Rate | Percentage of participants who are alive up to five years after receipt of protocol therapy. | Up to 5 years |
| Response Rate | Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement. |
Not provided
Inclusion Criteria:
Previously untreated, histologically confirmed mantle cell lymphoma.
Measurable or evaluable disease.
All stages are eligible.
Age > 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
Adequate hepatic function:
Serum creatinine < 1.5 mg/Dl.
Ability to give informed consent.
Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study.
Life expectancy greater than 6 months.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Izidore S. Lossos, MD | University of Miami Sylvester Comprehensive Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20038221 | Result | Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalon MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. doi: 10.3109/10428190903518345. | |
| 33735476 |
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| ID | Title | Description |
|---|---|---|
| FG000 | R-MACLO-IVAM-T | Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | R-MACLO-IVAM-T | Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide. |
| 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 Rate | Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 5 years |
|
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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 | R-MACLO Cycles | Adverse Events occurring during the combination Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (R-MACLO) treatment cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia (Grade 3-4) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Izidore Lossos MD | University of Miami | 305-243-4785 | ilossos@med.miami.edu |
Not provided
| 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 |
|---|---|
| D000069283 | Rituximab |
| D003520 | Cyclophosphamide |
| D003561 | Cytarabine |
| D004317 | Doxorubicin |
| D005047 | Etoposide |
| D007069 | Ifosfamide |
| D002955 | Leucovorin |
| D008727 | Methotrexate |
| D013792 | Thalidomide |
| D014750 | Vincristine |
| D015080 | Mesna |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D017829 | Granisetron |
| D002123 | Calcium Dobesilate |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Cyclophosphamide | Drug | Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes. |
|
|
| Cytarabine | Drug | Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4. |
|
|
| Doxorubicin | Drug | Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3 |
|
|
| Etoposide | Drug | Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4 |
|
|
| Ifosfamide | Drug | Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4 |
|
|
| Leucovorin | Drug | Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3. |
|
|
| Methotrexate | Drug | Methotrexate 1,200 mg/m2 in 250 cc 5 percent dextrose in water (D5W) IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3. |
|
|
| Thalidomide | Drug | Maintenance therapy. |
|
|
| Vincristine | Drug | Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3. |
|
|
| Mesna | Drug | Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4 |
|
|
| Filgrastim (G-CSF) | Drug | G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4) |
|
|
| Granisetron | Drug | Granisetron 1 mg IV on Day 1, Cycle 1 and 3 |
|
|
| Decadron | Drug | Decadron 10 mg IV on Day 1, Cycles 1 and 3 |
|
|
| Up to 5 years |
| Number of Patients Experiencing Adverse Events. | Number of patients experiencing adverse events during the course of protocol therapy. | Up to 5 years |
| Derived |
| Alderuccio JP, Saul EE, Iyer SG, Reis IM, Alencar AJ, Rosenblatt JD, Lossos IS. R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results. Am J Hematol. 2021 Jun 1;96(6):680-689. doi: 10.1002/ajh.26163. Epub 2021 Apr 7. |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Overall Survival Rate | Percentage of participants who are alive up to five years after receipt of protocol therapy. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 5 years |
|
|
|
| Secondary | Response Rate | Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement. | Participants who completed at least two cycles of therapy. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 5 years |
|
|
|
| Secondary | Number of Patients Experiencing Adverse Events. | Number of patients experiencing adverse events during the course of protocol therapy. | Posted | Number | participants | Up to 5 years |
|
|
|
| 21 |
| 22 |
| 22 |
| 22 |
| EG001 | R-IVAM Cycles | Adverse Events occurring during the Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (R-IVAM) treatment cycles. | 21 | 22 | 22 | 22 |
| EG002 | Thalidomide Therapy | Adverse Events occurring during Thalidomide maintenance therapy. | 19 | 20 | 19 | 20 |
| Anemia (Grade 3-4) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombocytopenia (Grade 3-4) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile neutropenia (Grade 3-4) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection (Grade 3-4) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Bacteremia (Grade 3-4) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis (Grade 3-4) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea (Grade 3-4) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (Grade 3-4) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pleural effusion (Grade 3-4) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness (Grade 3-4) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripheral Neuropathy (Grade 3-4) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Erectile Dysfunction (Grade 3-4) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anemia (Grade 1-2) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombocytopenia (Grade 1-2) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile Neutropenia (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Bacteremia (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Hyperglycemia (Grade 1-2) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypokalemia (Grade 1-2) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated creatinine (Grade 1-2) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea (Grade 1-2) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation (Grade 1-2) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (Grade 1-2) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pleural Effusion (Grade 1-2) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash (Grade 1-2) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Somnolence (Grade 1-2) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripheral Neuropathy (Grade 1-2) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Erectile Dysfunction (Grade 1-2) | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bradycardia (Grade 1-2) | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
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| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008228 | Lymphoma, Non-Hodgkin |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and 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 |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
| D010078 | Oxazines |
| 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 |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D054833 | Isoindoles |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D007191 | Indazoles |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
| Title | Measurements |
|---|---|
|
| 4-year overall survival rate |
|
| 5-year overall survival rate |
|