ALL Adult Consortium Trial: Adult ALL Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 15
- 主要终点
- Asparaginase Completion Rate
研究概览
简要总结
The purpose of this study is to determine the safety and effectiveness of a multi-drug chemotherapy regimen in adult patients with Acute Lymphoblastic Leukemia (ALL). We will use a regimen that is often used in pediatric patients and we will add drugs called PEG-asparaginase and E. coli asparaginase. PEG-asparaginase has been given as an injection in the past and has been used in treatment with both children and adults with ALL. Information from those other research studies suggests that intravenous PEG-asparaginase has been administered safely in both children and adults. We hope to gain more information about the participants disease and how it responds to standard chemotherapy drugs used to treat ALL>
详细描述
- This study has several periods of treatment called phases and uses several different drugs in each phase. The drugs may be given by mouth, into a vein, or into the spinal fluid (called intrathecal chemotherapy). In some individuals this treatment helps prevent leukemia cells from coming back in the spinal fluid and brain. Radiation therapy will also be administered as part of this treatment regimen.
- The treatment program consists of 2-different treatment arms with six separate phases of therapy. The phases of treatment are: (1) Steroid prophase (2) Induction (3) Consolidation I (4) Central nervous system (CNS) therapy (5) Consolidation II (6) Continuation.
- The participants treatment arm will depend on the status of their leukemia at the end of the induction therapy (the second phase of treatment). Arm A: all participants who achieve complete remission after Induction and Arm B: all participants who fail to achieve a complete remission after Induction.
- Steroid Prophase: All participants are involved in this treatment phase which consists of two drugs, one given intravenously (IV) and one given intrathecally. This phase lasts 3 days and the purpose is to collect scientific data that might be useful in the future and to see how steroids work in treating leukemia
- Induction: This phase begins immediately after the steroid prophase and lasts about 1 month. Induction is used to cause a remission. Eight drugs are used during this phase of treatment, and administration is either orally, IV or intrathecal. On day 29, participant's bone marrow and peripheral blood counts will be tested. If they have achieved complete remission or partial remission, they will proceed to the next phase of treatment. If they are not in complete remission, they will receive vincristine by IV on days 32, 39 and 46, until complete remission is achieved. If they do not achieve complete or partial remission by day 53 they will be removed from the study.
- Consolidation I: This phase of treatment begins as soon as there is a documented confirmation that the participant's leukemia is either in complete or partial remission. Treatment in this phase lasts about 7 weeks and is intended to further reduce the number of leukemia cells in the body. This consolidation treatment consists of 3 phases: 1A, 1B and 1C. Each phase involves a three week cycle of chemotherapy. Arm A and Arm B will be assigned according to remission status after induction therapy and will determine the order that the participant follows the Consolidation phases.
- Central Nervous System (CNS) Therapy: CNS therapy begins 3 weeks after the end of Consolidation I therapy and should last 3 weeks. Treatment includes a series of lumbar punctures with the administration of anti-leukemia drug as well as oral drugs and IV drugs. Radiation therapy will also be given during this phase of therapy. The purpose of radiation therapy is to prevent leukemia from coming back in the brain. Radiation therapy will be given in either 8 or 10 daily treatments.
- Consolidation II Therapy: This phase begins as soon as CNS therapy ends and lasts about 27-30 weeks. It consists of cycles of chemotherapy repeated every three weeks along with IV PEG-asparaginase administered every 3 weeks. The cycles will be repeated until the participant receives a total of 10 doses of asparaginase.
- Continuation Therapy: This phase begins after the end of the Consolidation II phase. The goal of this phase is to get rid of all leukemia in the body. It consists of cycles of chemotherapy repeated every three weeks and will last until the participant has been in remission for two years.
- During all phases of treatment, participants will have tests and procedures to monitor their health and for research purposes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8)
- •Age 18.00-50.99 years
排除标准
- •Prior anti-leukemic therapy except 1 week or less of steroids, and/or emergent radiation therapy to the mediastinum, or hydroxyurea or emergent leukopheresis
- •Known HIV positive
- •Secondary ALL
- •Pregnant or breast feeding women
- •Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely
研究组 & 干预措施
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Doxorubicin (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Cytarabine (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Methotrexate (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Vincristine (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Cyclophosphamide (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Methylprednisone (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Hydrocortisone Sodium Succinate (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Dexamethasone (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: 6-MP (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: PEG-Asparaginase (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Imatinib (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Etoposide (Drug)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Radiation Therapy (Procedure)
Pre-amendment cohort, 2500 IU/m2 q2 weeks
The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: E. coli Asparaginase (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Doxorubicin (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Cytarabine (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Methotrexate (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Vincristine (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Cyclophosphamide (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Methylprednisone (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Hydrocortisone Sodium Succinate (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Dexamethasone (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: 6-MP (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: PEG-Asparaginase (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Imatinib (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Etoposide (Drug)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: Radiation Therapy (Procedure)
Post-amendment cohort, 2000 IU/m2 q3 weeks
The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
干预措施: E. coli Asparaginase (Drug)
结局指标
主要结局
Asparaginase Completion Rate
时间窗: Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.
Feasibility based on the rate of asparaginase completed defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete \>25 weeks of IV PEG asparaginase as part of intensification therapy. Complete remission is defined as an interpretable bone marrow (a specimen with normal marrow elements present) with fewer than 5% lymphoblasts and peripheral blood without lymphoblasts, and an antigen presenting cell (APC) \> 1000/mm3 and platelets \> 100,000/mm3, and no evidence of extramedullary leukemia.
Number of Participants With Grade 3 or Worse Toxicity.
时间窗: Assessed on an ongoing basis (at least once every 3 months) while on study, including the treatment phases of Induction, Consolidation I & II, CNS, and Continuation. Treatment duration for this study was a median (range) of 287 days (2-974).
Defined as the number of participants who experience the following grade 3 or worse adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) v3: Neutrophils, Platelets, Febrile neutropenia, Infection, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Bilirubin, Liver dysfunction/failure, Hyperglycemia, Stomatitis, CNS hemorrhage, Thrombosis, Seizure, Osteonecrosis, Hypersensitivity, Pancreatitis, Neuropathy.
次要结局
- Complete Remission Rate(3-day Steroid prophase and 4-week induction treatment period. Participants are assessed on Day 32 of induction.)
- 3-year Overall Survival(Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (up to 5 years). Relevant for this measure is 3 years from the date of study entry.)
- 3-year Disease Free Survival(Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (up to 5 years). Relevant for this measure is 3 years from the date of complete remission.)
研究者
Daniel J. DeAngelo, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute