Hyper-CVAD Plus Nelarabine in Untreated T-ALL/Lymphoblastic Lymphoma
Overview[ - collapse ][ - ]
| Purpose | The goal of this clinical research study is to learn the effectiveness of intensive chemotherapy given in combination with nelarabine (followed by maintenance therapy) in the treatment of patients with T cel ALL and T cell lymphoblastic lymphoma. The safety of this treatment will also be studied. |
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| Condition | Leukemia Lymphoblastic Lymphoma Leukemia, Lymphoblastic, Acute |
| Intervention | Drug: Doxorubicin Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Methotrexate Drug: Vincristine Drug: Nelarabine |
| Phase | Phase 2 |
| Sponsor | M.D. Anderson Cancer Center |
| Responsible Party | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier | NCT00501826 |
| First Received | July 12, 2007 |
| Last Updated | April 25, 2014 |
| Last verified | April 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | July 12, 2007 |
|---|---|
| Last Updated Date | April 25, 2014 |
| Start Date | July 2007 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Complete Remission (CR) Rate [Time Frame: 3 Years] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Hyper-CVAD Plus Nelarabine in Untreated T-ALL/Lymphoblastic Lymphoma |
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| Official Title | Phase II Study of Hyper-CVAD Plus Nelarabine in Previously Untreated T-ALL and Lymphoblastic Lymphoma |
| Brief Summary | The goal of this clinical research study is to learn the effectiveness of intensive chemotherapy given in combination with nelarabine (followed by maintenance therapy) in the treatment of patients with T cel ALL and T cell lymphoblastic lymphoma. The safety of this treatment will also be studied. |
| Detailed Description | The intensive chemotherapy (hyper-CVAD therapy) used in this study includes a combination of 7 chemotherapy drugs. These drugs include Adriamycin (doxorubicin), cyclophosphamide, cytarabine (Ara-C), dexamethasone, methotrexate, nelarabine, and vincristine. The maintenance therapy used in this study includes a combination of 5 chemotherapy drugs. These drugs include L-asparaginase, methotrexate, prednisone, 6-mercaptopurine, and vincristine. Ara-C is designed to insert itself into DNA (the genetic material of cells) and stop the DNA from repairing itself. Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. Dexamethasone, doxorubicin, methotrexate, prednisone, and 6-mercaptopurine are each designed to stop or slow the growth of cancer cells, which may cause the cells to die. Nelarabine is designed to inhibit ("turn off") the growth and division of cancer cells. Vincristine is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. If you are found to be eligible to take part in this study, you will receive 2 kinds of intensive chemotherapy regimens (hyper-CVAD therapy and methotrexate plus Ara-C) that will alternate for a total of 8 courses (4 courses each). One (1) course of therapy is between 21 and 28 days. All chemotherapy will be given through a large vein by a central venous catheter. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. Intensive Chemotherapy: Hyper-CVAD therapy will be given during Courses 1, 3, 5, and 7. For this therapy, you will receive cyclophosphamide by vein over 2-3 hours every 12 hours for a total of 6 doses. It will be given over 3 days (Days 1, 2, and 3). You will receive doxorubicin by vein over 24 hours on Day 4. The doxorubicin infusion may be extended up to 48 hours, if you are considered to have poor heart function (provided this is known) because you may tolerate this drug better as a slow continuous infusion. You will receive vincristine by vein over 15-30 minutes on Days 4 and 11. You will receive dexamethasone 1 time a day by mouth or by vein over a few minutes on Days 1-4 and Days 11-14. You will also receive G-CSF (Filgrastim) by vein over a few minutes or just under the skin starting about 24-72 hours after the completion of each course of chemotherapy and until your white blood cell count has recovered (which will help with rapid recovery of normal bone marrow). For participants 60 years or older, this first course of chemotherapy will be given in a protective isolation room for monitoring by study staff to help watch for and decrease the risk of infections. Methotrexate will be given in combination with Ara-C during Courses 2, 4, 6, and 8. You will receive methotrexate by vein over 24 hours on Day 1. You will receive Ara-C by vein on Days 2-3, over 2-3 hours every 12 hours for a total of 4 doses. Doses of Ara-C will be adjusted according to the level of methotrexate you receive. Blood (about 1 teaspoon) will be drawn to measure the study drug level. Leucovorin, used to help decrease the side effects of methotrexate, will be given by vein (over 15 minutes) or by mouth (every 6 hours) for 2-3 days (or until the blood level of methotrexate is low enough to stop leucovorin). Filgrastim will be given at the same dose and schedule as during Courses 1, 3, 5, and 7. During treatment, you will have a physical exam, including measurement of your vital signs. You will have blood drawn (about 1 tablespoon each) at least once a week and sometimes up to 3 times a week. After 1 or 2 courses of chemotherapy, the tests done during the screening visit will be repeated to check for disease response to treatment. A bone marrow biopsy will be repeated starting at 2 weeks into therapy. This biopsy will be repeated about every week until the disease response to treatment is known. If the leukemia or lymphoma is responding to therapy and you have not experienced any intolerable side effects, you will continue on therapy for up to 8 courses. You will be taken off this study if the disease gets worse or you experience any intolerable side effects. To decrease the risk that leukemia will develop in the brain, you will be given treatment to the brain by an injection into your spinal fluid with methotrexate around Day 2. Ara-C will be given by an injection into your spinal fluid on about Day 7 of the course. The total number of these treatments may be up to 8, which means that you will have 2 with each course until the total number of these treatments is reached. During Courses 5 and 6 (when you receive nelarabine), injections into your spinal fluid will be given later (around Days 15 and 22 of each course). An Ommaya reservoir may also be surgically placed as a route to treat leukemia in the brain or to decrease the risk of leukemia in the brain. It would be placed in participants 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. After the first 4 courses, you will receive 1 course of nelarabine. Nelarabine will be given by vein over 2 hours once a day for 5 days. After about 21-35 days, you will continue with Course 5 (Hyper-CVAD). After Course 5, you will receive a second course of nelarabine at the same dose and schedule as before. Once this course is complete, you will continue with Course 6 (methotrexate and cytarabine). After completion of the treatment, you will have a complete physical exam, including measurement of your vital signs. You will have blood drawn (about 8 teaspoons) for routine tests. You will have a chest x-ray or CT scans performed, if needed. You may have a bone marrow biopsy repeated. If you had enlarged lymph glands in the center of the chest, you may receive radiation to the chest. If you do not need radiation, you will proceed with monthly maintenance chemotherapy. If you did require radiation (based on what your doctor thinks is best), you will start maintenance chemotherapy after finishing radiation. Maintenance Therapy: Maintenance chemotherapy will be given for a total of 30 months and will be interrupted by 2 periods of intensive chemotherapy courses. For maintenance therapy, you will receive 6-mercaptopurine by mouth up to 3 times a day, methotrexate by mouth once a week, vincristine by vein once a month over a few minutes, and prednisone by mouth once a day for 5 days in a row every month. The first period of intensive chemotherapy courses will be given at Courses 6 and 7 into the maintenance program. For the intensive chemotherapy at this time, you will receive nelarabine by vein over 2 hours once a day for 5 days in a row for about 21-35 days apart from each other. The second period of intensive chemotherapy courses will be given at Courses 18 and 19. It will start first with methotrexate by vein on Day 1 and L-asparaginase by vein on Day 2. These will be given once a week for 4 doses. The following month, you will receive hyper-CVAD (like during Course 1 at the very beginning of treatment). The hyper-CVAD may begin before the combination of methotrexate and L-asparaginase. Intensive chemotherapy will be given on an inpatient or outpatient basis (depending on what the study doctor thinks is safe) for the 8 intensive cycles of chemotherapy. The maintenance treatments may be given on an outpatient basis. However, under some circumstances (such as intolerance to intensive chemotherapy), you may be moved from the intensive chemotherapy to the maintenance phase before the completion of 8 cycles of intensive chemotherapy or without having received nelarabine. After completion of all therapy, you will return every 3-6 months for a checkup. You may have x-rays repeated, if needed. If you have a complete remission, you will have bone marrow biopsies repeated about every 4 months to evaluate the marrow for "minimal residual disease," which is the presence or absence of very small amounts of leukemia that cannot be usually detected by routine blood tests. This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. Their use together in this study is investigational and for use in research only. Up to 60 patients will take part in this study. All will be enrolled at MD Anderson. |
| 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 |
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| Intervention | Drug: Doxorubicin Hyper-CVAD (odd courses 1, 3, 5, 7): 50 mg/m^2 IV over 24 hours on day 4 after last dose of Cyclophosphamide (CTX) Other Names:
Hyper-CVAD (odd courses 1, 3, 5, 7): 300 mg/m^2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2). Other Names:
High-dose Methotrexate plus cytarabine (even courses 2, 4, 6, 8): Cytarabine 3 gm/m^2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 Other Names:
Hyper-CVAD (odd courses 1, 3, 5, 7): 40 mg IV or by mouth (PO) daily days 1-4 and 11-14. Other Names: DecadronDrug: Methotrexate High-dose Methotrexate plus cytarabine (even courses 2, 4, 6, 8): 200 mg/m^2 IV over 2 hours followed by 800 mg/m^2 over 22 hours on day 1. Drug: Vincristine Hyper-CVAD (odd courses 1, 3, 5, 7): 2 mg IV days 4 and 11 (+/- 2 days) Drug: Nelarabine 650 mg/m^2 IV over 2 hours daily x 5 days every 21 to 35 days x 2 courses. Other Names: Arranon |
| Study Arm (s) | Experimental: Hyper-CVAD + Nelarabine Intensive chemotherapy (hyper-CVAD therapy) includes combination of 7 chemotherapy drugs: Adriamycin (doxorubicin), cyclophosphamide, cytarabine (Ara-C), dexamethasone, methotrexate, nelarabine, and vincristine. |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 60 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | July 2016 |
| Eligibility Criteria | Inclusion Criteria: 1. Previously untreated T cell ALL including T cell lymphoblastic lymphoma. Failure to one induction course of chemotherapy are eligible. Patients in CR after are also eligible. 2. ECOG performance status less than or equal to 3. 3. Serum bilirubin less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 5.0 mg/dL is acceptable. SGOT or SGPT less than or equal to 4 x ULN. 4. Serum creatinine less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 2.5 mg/dL is acceptable. Exclusion Criteria: 1) Pregnant or nursing women. |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Farhad Ravandi-Kashani, MD 713-745-0394 |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00501826 |
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| Other Study ID Numbers | 2006-0328 |
| Has Data Monitoring Committee | No |
| Information Provided By | M.D. Anderson Cancer Center |
| Study Sponsor | M.D. Anderson Cancer Center |
| Collaborators | GlaxoSmithKline |
| Investigators | Principal Investigator: Farhad Ravandi-Kashani, M.D. M.D. Anderson Cancer Center |
| Verification Date | April 2014 |
Locations[ + expand ][ + ]
| UT MD Anderson Cancer Center | Houston, Texas, United States, 77030 Recruiting |
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