Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
2021年9月21日 更新者：ERYtech Pharma
An Escalating Dose Phase IIa Study of L-Asparaginase Encapsulated in Erythrocytes (GRASPA®) in Association With Polychemotherapy During Induction Phase for Treatment of Elderly Patients With Acute Lymphoblastic Leukaemia (ALL), Aged 55 Years and Over, With Philadelphia Chromosome-negative (ALL Ph-)
The main purpose of this study is to determine the maximum tolerated and efficient dose of GRASPA® in combination with polychemotherapy treatment of elderly patients with ALL, 55 years and over, Philadelphia chromosome-negative (ALL Ph-).
調査の概要
詳細な説明
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over.
Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses.
GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
研究の種類
介入
入学 (実際)
30
段階
- フェーズ2
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
55年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Patient aged ≥55 years old
- With newly diagnosed ALL without prior treatment
- Capable to receive polychemotherapy (World Health Organization (WHO) performance status ≤2)
- With or without meningeal disease
- Having signed an Informed Consent Form
- Subscribed to social security insurance
Exclusion Criteria:
- ALL translocation(9;22) and/or BCR-ABL (Breakpoint Cluster Region-Abelson) positive
- Performance status incompatible with chemotherapy treatment (WHO score >2)
Patient presenting with a general or visceral contraindication to intensive treatment including :
- Cardiac insufficiency defined as Left Ventricular Ejection Fraction <50% of the theoretical value
- Plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges, except if related to ALL
- Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) levels 5 times greater than the upper limit of laboratory ranges, except if related to ALL
- Patient with another evolutive cancer other than ALL
- Severe evolutive infection, or Human Immunodeficiency Virus (HIV) seropositive or, active hepatitis related to B or C viral infection
- Prior treatment with L-asparaginase (irrespective of the form)
- History of grade 3 transfusional incident (life threatening)
- Patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible Red Blood Cells Concentrate
- Patient included in another clinical trial during the last 4 weeks
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：GRASPA 50 IU/kg
Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase.
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
実験的：GRASPA 100 IU/kg
Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
実験的：GRASPA 150 IU/kg
Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
時間枠：7 days after the first administration of GRASPA® during Induction 1
|
The main evaluation criterion is a composite efficacy/toxicity criterion.
Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA®
|
7 days after the first administration of GRASPA® during Induction 1
|
|
Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
時間枠：Induction 1 and Induction 2
|
Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities.
|
Induction 1 and Induction 2
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Plasma Concentrations of Asparagine
時間枠：Induction 1 & Induction 2
|
Mean plasma concentration of asparagine over time.
Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L.
|
Induction 1 & Induction 2
|
|
Plasma Concentrations of Aspartic Acid
時間枠：Induction 1 and Induction 2
|
Mean plasma concentration of aspartic acid over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamine
時間枠：Induction 1 and Induction 2
|
Mean glutamine concentration over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamic Acid.
時間枠：Induction 1 and Induction 2
|
Mean glutamic acid concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Asparagine
時間枠：Induction 1 and Induction 2
|
Mean cerebral spinal fluid asparagine concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Aspartic Acid
時間枠：Induction 1 and Induction 2
|
Mean cerebral spinal fluid aspartic acid concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamine
時間枠：Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamine concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamic Acid
時間枠：Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamic acid concentration
|
Induction 1 and Induction 2
|
|
Summary of Free Asparaginase Over Time
時間枠：Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Summary of Encapsulated Asparaginase (U/L) Over Time
時間枠：Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Number of Patients Positive for Anti-L-asparaginase Antibodies
時間枠：Induction 1 and Induction 2
|
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
|
Induction 1 and Induction 2
|
|
Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
時間枠：1 and 2 months
|
CR was defined using:
|
1 and 2 months
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Mathilde Hunault-Berger, Professor、University Hospital, Angers
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年4月1日
一次修了 (実際)
2011年1月1日
研究の完了 (実際)
2012年10月1日
試験登録日
最初に提出
2012年1月16日
QC基準を満たした最初の提出物
2012年1月30日
最初の投稿 (見積もり)
2012年2月1日
学習記録の更新
投稿された最後の更新 (実際)
2021年10月15日
QC基準を満たした最後の更新が送信されました
2021年9月21日
最終確認日
2018年6月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。