Leukemia, Lymphocytic, Acute
Conditions
Keywords
Acute lymphoblastic leukemia, ALL, Leukemia, Methotrexate, Vincristine, PEG-l-asparaginase, PEG asparaginase, Pegaspargase, Oncaspar, Polyethylene Glycol Conjugated Lasparaginase-H, Dexamethasone, Decadron, Rituximab, Rituxan
Brief summary
This goal of this clinical research study is to learn if the combination of methotrexate, pegylated-L-asparaginase, vincristine, and dexamethasone (also rituximab in some patients) can help to control ALL that has not responded to previous treatment or has come back after a response or chronic myeloid leukemia (CML).
Detailed description
The Study Drugs: Methotrexate is designed to disrupt cells from making and repairing DNA (the genetic material of cells) and copying themselves. 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. Pegylated-L-asparaginase is designed to get rid of an important building block of proteins in leukemia cells. Dexamethasone is a steroid that causes the leukemia cells to breakdown. Rituximab is designed to attach to lymphoma cells, which may cause them to die. Study Drug Administration: If you are found to be eligible to take part in this study, you will receive methotrexate through a needle in your vein on Days 1 and 15 (+/- 2 days) over 2 hours. You will receive vincristine by vein on Days 1, 8 and 15 (+/- 2 days) over 30 minutes. You will receive pegylated-L-asparaginase by vein on Days 2 and 16 (+/- 2 days) over about 2 hours. You will receive dexamethasone by vein over about 30 minutes or by mouth on Days 1-4 and 15-18 (+/- 2 days). If leukemia cells have a protein called cluster of differentiation antigen 20 (CD20), you will also receive rituximab by vein on Days 1 and 15 of Cycles 1-4 (+/- 2 days) over about 2-8 hours. Each cycle will be at least 28 days. If you have Philadelphia positive ALL, you may continue to receive a tyrosine kinase inhibitor (TKI). Examples of TKIs include Imatinib, Dasatinib, and Nilotinib. If you are not taking a TKI, you may begin taking a TKI. Your doctor will describe treatment with TKIs with you in more detail. Once your blood counts improve and your leukemia is under control your doctor may decide to continue on treatment every 4-6 weeks. If your leukemia is not under control after the first cycle, your doctor may decide to start the next cycle without your blood counts improving. Study Visits: During Cycle 1, blood (about 2 teaspoons) will be drawn at least 1 time each week for routine tests. If the doctor thinks it is necessary, you may be asked to have additional blood drawn. Between Days 14-28 of Cycle 1, you will have a bone marrow aspirate to check the status of the disease. This test may be delayed or repeated if your doctor does not think you are in remission. Since pegylated-L-asparaginase can cause problems with blood clotting and inflammation of the pancreas, on Days 2 and 16 of All cycles, blood (about 2 teaspoons) will be drawn to check how well your blood clots and to check the health of your pancreas. During Cycles 2- 6, blood (about 2 teaspoons) will be drawn for routine tests at least 2 times each month. If the doctor thinks it is necessary, you may have a bone marrow aspirate to check the status of the disease. Length of Study: You may receive the study drugs for up to 6 cycles. You will be taken off study early if the disease gets worse, you experience intolerable side effects, or your doctor thinks that it is no longer in your best interest to receive the study drug(s). This is an investigational study. Methotrexate, pegylated-L-asparaginase, and vincristine are all FDA approved for use in ALL. Dexamethasone is FDA approved as a steroid and steroids are traditionally an important part of treatment of leukemia. Rituximab is FDA approved for the treatment of non-Hodgkin's lymphoma. The combination of all these drugs is investigational. Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGMethotrexate
200 mg/m\^2 by vein on days 1 and 15.
DRUGVincristine
1.4 mg/m\^2 by vein (maximum dose 2 mg) on days 1, 8 and 15.
2500 International units/m\^2 by vein on days 2 and 16
DRUGDexamethasone
40 mg by vein or by mouth daily days 1-4 and 15-18.
DRUGRituximab
Rituximab 375 mg/m\^2 by vein on days 1 and 15 (first 4 cycles) for patients CD20 positive or positive by immunostain.
Sponsors
Leadiant Biosciences, Inc.
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Previously treated ALL (including Burkitt's lymphoma) or lymphoblastic lymphoma in relapse or primary refractory; without viable stem cell transplant option. Patients with previously treated Philadelphia chromosome positive ALL will be also eligible; 2. Chronic myeloid leukemia in blast phase 3. Zubrod performance status \</= 3; 4. Adequate liver function (bilirubin \</= 3.0mg/dl, unless considered due to tumor),and renal function (creatinine \</= 3.0 mg/dl unless considered due to tumor; 5. Age \>/= to 1 year 6. Understand and voluntarily sign an informed consent form. 7. For pediatric patients (age \>/= 1 year to \</= 18 years), Lansky performance status \>/=50 8. For pediatric patients (age \>/= 1 year to \</= 18 years), second or greater relapse
Exclusion criteria
1. Pregnant patients 2. Prior history of allergic reaction, serious pancreatitis, hemorrhagic or thrombotic event with PEG-l-asparaginase or its components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | 6 cycles (cycle = 28 days) | Rate calculated as number of participants with CR. Complete Remission (CR) defined as Normalization of peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above and platelet count of 100 x 10\^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: March 6, 2009 to May 6, 2013. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| MOAD Chemotherapy regimen of methotrexate, rituximab, vincristine, pegylated L-asparaginase and dexamethasone (MOAD). Methotrexate 200 mg/m\^2 intravenous (IV) days 1 and 15, Vincristine 1.4 mg/m\^2 IV days 1, 8 and 15; PEG-l-asparaginase 2500 International units/m\^2 IV days 2 and 16; Dexamethasone 40 mg/day IV or oral days 1-4 & 15-18; Rituximab 375 mg/m\^2 IV days 1 & 15 (first 4 cycles) for participants CD20 positive or positive by immunostain. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MOAD |
|---|---|
| Age, Continuous | 42 years |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 37 / 37 |
| serious Total, serious adverse events | 33 / 37 |
Outcome results
Primary
Complete Response (CR) Rate
Rate calculated as number of participants with CR. Complete Remission (CR) defined as Normalization of peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above and platelet count of 100 x 10\^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR.
Time frame: 6 cycles (cycle = 28 days)
Population: Of the 37 participants enrolled, 36 participants completed therapy and were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOAD | Complete Response (CR) Rate | 28 percentage of participants |