Modified Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) Program for Acute Lymphoblastic Leukemia
Overview[ - collapse ][ - ]
| Purpose | The goal of this clinical research study is to learn if intensive chemotherapy (with monoclonal antibody therapy in some patients) given for 8 courses over 5 to 6 months followed by monthly maintenance chemotherapy for 2 ½ years can improve or cure acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. |
|---|---|
| Condition | Leukemia Acute Lymphoblastic Leukemia |
| Intervention | Drug: Rituximab Drug: Cyclophosphamide (CTX) Drug: Doxorubicin Drug: Vincristine Drug: Dexamethasone Drug: Methotrexate (MTX) Drug: Cytarabine Drug: G-CSF Drug: Mesna Drug: Pegylated asparaginase Drug: Pegfilgrastim Drug: Solumedrol |
| Phase | Phase 2 |
| Sponsor | M.D. Anderson Cancer Center |
| Responsible Party | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier | NCT00671658 |
| First Received | April 30, 2008 |
| Last Updated | August 23, 2013 |
| Last verified | August 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | April 30, 2008 |
|---|---|
| Last Updated Date | August 23, 2013 |
| Start Date | November 2002 |
| Estimated Primary Completion Date | July 2013 |
| Current Primary Outcome Measures | Overall Response Rate [Time Frame: Response assessed following first 21 day course] [Designated as safety issue: No]ALL Response: Complete remission (CR) - Normalization peripheral blood & bone marrow 5% or < blasts in normocellular or hypercellular marrow granulocyte count of 1 x 109/L or > & platelet count >100 x 109/L. CR with incomplete platelet recovery (CRp)- per CR but platelet count <100 x 109/L. CR with incomplete recovery (CRi) - per CR but platelet count <100 x 109/L or absolute neutrophil count < 1 x 109/L. Partial response (PR) - As above except for presence of 6-25% marrow blasts. Lymphoblastic lymphoma (& ALL subtypes with extramedullary disease): CR - disappearance of all known disease. PR - >50% decrease in tumor size using sum of product, includes 50% volume decrease in lesions measurable in 3 dimensions. No Response (NR) - No significant change (includes stable disease). Lesions decreased size but <50% or lesions with slight enlargement <25% increase in size. Progressive Disease (PD) - Appearance of new lesions, 25% or > increase in size existing lesions (>50% if 1 lesion & <2). |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Modified Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) Program for Acute Lymphoblastic Leukemia |
|---|---|
| Official Title | Phase II Study of The Modified Hyper-CVAD Program for Acute Lymphoblastic Leukemia |
| Brief Summary | The goal of this clinical research study is to learn if intensive chemotherapy (with monoclonal antibody therapy in some patients) given for 8 courses over 5 to 6 months followed by monthly maintenance chemotherapy for 2 ½ years can improve or cure acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. |
| Detailed Description | The modified hyper-CVAD regimen is a combination of chemotherapy drugs including cyclophosphamide, vincristine, Adriamycin, dexamethasone and pegylated asparaginase given together for one "course" of treatment. This alternates with a course or combination of the chemotherapy drugs methotrexate, cytarabine (ara-C), and pegylated asparaginase. Rituximab is a protein (monoclonal antibody) that attaches to the surface of the leukemia or lymphoma cells, which have a marker, called "CD20". Before treatment starts, participants will have a complete physical exam, including blood (about 8 teaspoons) tests. A chest X-ray may be taken. CT scans may be taken if needed. A bone marrow sample will be taken through a large needle in the hipbone. Women able to have children must have a negative blood pregnancy test. An ECG (tracing of the heart) and a cardiac scan or echocardiogram may be taken to check the heart function. Participants will receive these 2 kinds of intensive chemotherapy courses for a total of 8 courses as long as they are able to tolerate them. Chemotherapy courses will be given through a large vein by a central venous catheter (a plastic tube usually placed under the collarbone) or a long-line catheter (a plastic tube usually placed in the upper arm). During treatment, participants will have a physical exam and undergo blood tests (about 1 tablespoon each) at least twice a week. After the first course of chemotherapy, the tests done before treatment will be repeated to check for response. In patients with acute lymphoblastic leukemia or lymphoblastic lymphoma with marrow disease, a bone marrow sample will be repeated about 2 and 3 weeks from the beginning of treatment to check the response. Course 1 (odd courses) will start by giving rituximab by vein over 6 hours on Day 1 and Day 11 for patients whose leukemia or lymphoma expresses CD20. Participants will receive the drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) 30-60 minutes before each dose of rituximab. This will be done to lessen the risk of fever, chills, and allergic reactions. Usually, the first dose of rituximab requires about 6 to 8 hours to complete. If side effects do occur during the infusion, participants will be observed for an additional 2 hours after the rituximab is given. Then, the cyclophosphamide will be given as described below. Other participants who do not have the CD20 marker will start Course 1 with cyclophosphamide given by vein over 2-3 hours every 12 hours. This will be given for 6 doses over 3 days (Days 1,2, and 3). Pegylated asparaginase will be given by vein over 30 minutes on Day 1. Adriamycin will be given by vein over 24 hours on Day 4. Vincristine will be given by vein over 15 to 30 minutes on Days 1 and 11. Dexamethasone (a steroid) will be given by mouth or by vein on Days 1 to 4 and 11 to 14. Pegfilgrastim (a growth colony stimulating factor) will be given after each course of chemotherapy is finished. It is given to help with rapid recovery of the white blood cells in the normal marrow. Pegfilgrastim will be injected under the skin within 72 hours of completion of each cycle of chemotherapy. Filgrastim, a shorter active form of pegfilgrastim may be used instead or added later if needed. Treatment to protect the brain will be given inside the spinal using lumbar punctures (spinal taps) with chemotherapy, including methotrexate around day 2 and cytarabine (ara-C) about day 7 of the course. This is done to decrease the risk that the leukemia or lymphoma will develop there. If there is leukemia or lymphoma in the spinal fluid at the time of the first spinal tap, then the treatments will be given more frequently. For patients aged 60 years or older, this first course of chemotherapy will be given in a protective isolation room to decrease the risk of infection(s). During Course 2, participants whose leukemia expresses CD20 will receive rituximab by infusion over 4 hours on Days 1 and 8. Other participants who do not have CD20 on the leukemia cells will start with methotrexate by vein over 24 hours on Day 1. Cytarabine (ara-C) will be given by vein over 2 hours every 12 hours for 4 doses (Days 2 and 3). Vincristine will be given by vein over 15 to 30 minutes on Days 1 and 8. Pegylated asparaginase will be given by vein over 30 minutes on Day 4 or 5 after the methotrexate has cleared (as checked by blood tests). Citrovorum factor (leucovorin), an antidote for side effects of methotrexate, will be given by vein or by mouth for 2-3 days (Day 2 and on). Pegfilgrastim will be given as in Course 1 (24-72 hours after the chemotherapy is finished). The treatment to protect the brain inside the spinal fluid will be given as in Course 1 on Days 2 and 7. The rest of the chemotherapy will switch between hyper-CVAD and pegylated asparaginase (Courses 3, 5, and 7) and methotrexate,cytarabine (ara-C), vincristine, and pegylated asparaginase (Courses 4, 6, and 8) to complete a total of 8 courses. Participants whose leukemia expresses CD20 will receive a total of 12 doses (2 per each of the first four courses, then one with the last four courses) of rituximab. After the 8 courses, patients with lymphoblastic lymphoma who had enlarged lymph glands in the mediastinum may receive radiation to the chest. Those participants not needing radiation will proceed to monthly maintenance chemotherapy. This includes daily 6-mercaptopurine taken by mouth, weekly methotrexate by vein or mouth, monthly vincristine by vein, and dexamethasone by mouth for 5 days every month. Participants with lymphoblastic lymphoma will start maintenance chemotherapy after finishing radiation. Maintenance chemotherapy will be given for a total of 30 months, and will be interrupted by 2 periods of intensive chemotherapy courses. The first will be at six months into the maintenance program starting first with hyper-CVAD (like Course 1) except without pegylated asparaginase). The following months, participants will receive methotrexate by vein on Day 1, vincristine by vein on Day 1, and pegylated asparaginase by vein on Day 2. Participants will receive this sequence of 2 chemotherapy courses again 18 months into the maintenance program. Participants with the CD20 marker will receive rituximab during the maintenance chemotherapy (with the vincristine during months 1, 3, 6, 7, 10, 13, 18 & 19). After one or two courses of therapy, the response to the treatment will be evaluated. If the leukemia or lymphoma is responding, the therapy will be continued. Participants will be taken off study if the leukemia or lymphoma starts to get worse. After completion of treatment, participants will have a complete physical exam, including blood tests (about 8 teaspoons). If needed, a chest X-ray or CT scan will be done. A bone marrow sample will be taken through a large needle. Patients will then return every 3 to 6 months for a checkup, including blood tests and bone marrow aspiration. X-rays may be repeated if needed. An Ommaya reservoir may also be placed surgically as a route to treat leukemia in the brain or to decrease the risk of leukemia in patients who have difficulty with the spinal treatments. An Ommaya reservoir is a tube inserted under the skin of the scalp that enters into the spinal fluid cavity of the brain. Treatment will be given on an inpatient basis for the 8 intensive cycles of chemotherapy, or as indicated by the clinical condition. The maintenance treatments will be given as an outpatient but may be given as an inpatient if needed. This is an investigational study. All of the drugs are commercially available. Their use together in this study is investigational. About 280 patients will take part in this study. All will be enrolled at M. D. Anderson Cancer Center. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
|
| Intervention | Drug: Rituximab 375 mg/m2 by vein Other Names: RituxanDrug: Cyclophosphamide (CTX) 300 mg/m2 by vein Other Names:
50 mg/m2 by vein Other Names:
2 mg by vein Other Names:
40 mg by vein or by mouth (P.O.) Other Names: DecadronDrug: Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 200 mg/m2 by vein followed by 800 mg/m2 for Courses 2,4,6,8 Other Names: RheumatrexDrug: Cytarabine 100 mg intrathecal for Courses 1,3,5,7 3 gm/m2 by vein for Courses 2,4,6,8 Other Names:
10 ug/kg subcutaneous injection Other Names:
600 mg/m2 a day by vein Other Names: MesnexDrug: Pegylated asparaginase 2000 International units/m2 by vein Other Names:
6 mg (flat dose) within 72 hrs after completion of chemotherapy Other Names:
40 mg by vein for Courses 2,4,6,8 Other Names:
|
| Study Arm (s) | Experimental: HYPER-CVAD Rituximab 375 mg/m2 by vein. Cyclophosphamide (CTX) 300 mg/m2 by vein. Doxorubicin 50 mg/m2 by vein. Vincristine 2 mg by vein. Dexamethasone 40 mg by vein or by mouth (P.O.). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m2 by vein followed by 800 mg/m2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m2 by vein for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m2 a day by vein. Pegylated asparaginase 2000 International units/m2 by vein. Pegfilgrastim 6 mg (flat dose) within 72 hrs after completion of chemotherapy. Solumedrol 40 mg by vein for Courses 2,4,6,8. |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 220 |
| Estimated Completion Date | July 2013 |
| Estimated Primary Completion Date | July 2013 |
| Eligibility Criteria | Inclusion Criteria: 1. Newly diagnosed, previously untreated ALL or lymphoblastic lymphoma, or having achieved CR with one course of induction chemotherapy. 2. Failure to one induction course of chemotherapy are eligible, but these patients will be analyzed separately. 3. All ages are eligible. 4. Zubrod performance less than or equal to 3 5. Adequate liver function (bilirubin renal function (creatinine 6. Adequate cardiac function as assessed by history and physical examination. 7. No active co-existing malignancy with life expectancy less than 12 months due to that malignancy. Exclusion Criteria: 1) N/A |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00671658 |
|---|---|
| Other Study ID Numbers | ID02-230 |
| Has Data Monitoring Committee | No |
| Information Provided By | M.D. Anderson Cancer Center |
| Study Sponsor | M.D. Anderson Cancer Center |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Susan O'Brien, M.D. M.D. Anderson Cancer Center |
| Verification Date | August 2013 |
Locations[ + expand ][ + ]
| UT MD Anderson Cancer Center | Houston, Texas, United States, 77030 |
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