Dose Escalation of Clofarabine in Combination With Cytarabine and Idarubicin as Induction Therapy in High Risk AML (CIARA)
2012年2月17日 更新者：Prof. Dr. Juergen Krauter、Hannover Medical School
Phase I/II Study on Cytarabine and Idarubicin Combined With Escalating Doses of Clofarabine as Induction Therapy in Patients With Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10)
With current chemotherapy protocols, in 60-80% of patients with acute myeloid leukemia (AML) the leukemic blasts in the bone marrow can be reduced to < 5%.
This is called "complete remission (CR)" and is the prerequisite for cure of the disease.
During the last years, several genetic and biologic risk factors for the achievement of CR have been defined, and the remission rates vary considerably between patient groups with different risk profiles.
On one hand, patients with certain chromosomal or molecular aberrations have very high CR rates of approximately 90%.
Moreover, in some of these patients, molecularly targeted therapies for specific genetic aberrations are currently evaluated in clinical trials.
However, these genetic aberrations account for only 50-60% of the overall patient population in AML.
The remaining patients have a significantly inferior CR rate of only 50-60% with 30% resistant disease after two cycles of standard induction chemotherapy.
In conclusion, there is need for improved induction regimens in a large number of adult patients with AML.
An improved CR rate in this patient population will increase the number of patients eligible for intensive consolidation such as an allogeneic stem cell transplantation and might thereby be the basis for a better overall outcome.
However, there is no clear evidence that this goal can be achieved with the currently available chemotherapy protocols.
Clofarabine (2-chloro-2-fluoro-deoxy-9-D-arabinofuranosyladenine) is a nucleoside analogon which combines properties of fludarabine and cladribine.
Due to the lack of neurological side effects, clofarabine could be explored in higher doses than other nucleoside analogues and has shown considerable antileukemic activity in patients with relapsed or refractory acute leukemias and elderly AML patients alone or in combination with cytarabine.
In addition, the combination of clofarabine, cytarabine and idarubicin has produced promising results with acceptable toxicity in patients with relapsed or refractory AML.
Based on these initial studies, there is need for a further optimization of the clofarabine dose in this combination.
The aim of the AMLSG 17-10 study is therefore to evaluate the tolerability and safety of increasing doses of clofarabine in combination with idarubicin/cytarabine in patients with high risk AML defined by the genetic and molecular risk profile.
調査の概要
研究の種類
介入
入学 (予想される)
60
段階
- フェーズ2
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
-
Düsseldorf、ドイツ、40225
- まだ募集していません
- Universitätsklinikum Düsseldorf
-
コンタクト：
- Andrea Kuendgen, MD
- メール：andrea.kuendgen@med.uni-duesseldorf.de
-
主任研究者：
- Andrea Kuendgen, MD
-
Essen、ドイツ、45239
- 募集
- Klinikum Essen-Werden
-
コンタクト：
- Mohammad Wattad, MD
- メール：m.wattad@kliniken-essen-sued.de
-
主任研究者：
- Mohammad Wattad, MD
-
Freiburg、ドイツ、D-79106
- 募集
- Universitatsklinikum Freiburg
-
コンタクト：
- Michael Luebbert, MD
- メール：luebbert@mm11.ukl.uni-freiburg.de
-
主任研究者：
- Michael Luebbert, MD
-
Hamburg、ドイツ、20246
- まだ募集していません
- Universitätsklinikum Hamburg-Eppendorf
-
コンタクト：
- Walter Fiedler, MD
- メール：fiedler@uke.uni-hamburg.de
-
主任研究者：
- Walter Fiedler, MD
-
Hannover、ドイツ、D-30625
- 募集
- Hannover Medical School
-
コンタクト：
- Juergen Krauter, MD
- 電話番号：+49-511-532-3720
- メール：Krauter.Juergen@MH-Hannover.de
-
主任研究者：
- Juergen Krauter, MD
-
Muenchen、ドイツ、81675
- まだ募集していません
- Klinikum rechts der Isar
-
コンタクト：
- Justus Duyster
- メール：justus.duyster@lrz.tum.de
-
主任研究者：
- Justus Duyster, MD
-
Ulm、ドイツ、89081
- まだ募集していません
- Universitätsklinikum Ulm
-
コンタクト：
- Richard Schlenk, MD
- メール：Richard.Schlenk@uniklinik-ulm.de
-
主任研究者：
- Richard Schlenk, MD
-
-
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
18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:
Patients with newly diagnosed AML according to WHO classification and aged ≥ 18 years eligible for an intensive induction chemotherapy with with the following characteristics:
- absence of a t(15;17), t(8;21), inv(16)/t(16;16) and the respective fusion transcripts PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11
- absence of an activating FLT3-mutation (FLT3-ITD or TKD-mutation)
- absence of an NPM1 exon12 mutation
- Written informed consent
- No previous cytotoxic chemotherapy for the treatment of AML (exception: oral hydroxyurea for up to 5 days during screening/baseline to control hyperleukocytosis)
Adequate renal and hepatic functions as indicated by the following laboratory values:
- Serum creatinine > upper limit of normal (ULN) or glomerular filtration rate (GFR) > 60 mL/min/1.73 m2, respectively
- Serum bilirubin < 1.5 x ULN
- Aspartate aminotransferase (AST/SGOT)/ alanine aminotransferase (ALT/SGPT) < 2.5 x ULN
- Alkaline phosphatase (ALP) < 2.5 x ULN
- Capable of understanding the investigational nature, potential risks and benefits of the study
- Women of childbearing potential must have a negative serum pregnancy test with a sensitivity of at least 25 MIU/ml within 72 hours prior to start of IMP treatment
Female patients must meet one of the following criteria:
- For female patients > 50 years of age at the day of inclusion: Menopause since at least 1 year
Female patients < 50 years of age at the day of inclusion who meet all of the following criteria:
- menopause since at least 1 year
- serum FSH levels > 40 MIU/mL
- serum estrogen levels < 30 pg/ml or negative estrogen test
- 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral ovariectomy with or without hysterectomy
- Correct use of two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 90 days after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom or condom) or with a spermicide. In case the patient takes hormone preparations for suppression of menstruation during the period of aplasia, a suitable and effective method of contraception has to be discussed with the investigator and used by the patient
- General sexual abstinence from the time of screening/baseline, during the study until a minimum of 90 days after the last administration of study medication
- Having only female sexual partners
- Monogamous relationship with sterile male partner
Male patients must meet one of the following criteria:
- 6 weeks after surgical sterilization by vasectomy
- Correct use of two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 90 days after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) or of an IUD with a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom or condom) or with a spermicide.
- General sexual abstinence from the time of screening/baseline, during the study until a minimum of 90 days after the last administration of study medication
- Having only male sexual partners
- Monogamous relationship with sterile female partner
Exclusion Criteria:
- Current concomitant chemotherapy, radiation therapy or immunotherapy not defined in the study protocol
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of oral hydroxyurea. The patient must have recovered from all non-hematological acute toxicities from any previous therapy
- Participation in a clinical trial within 30 days before inclusion in this study or concurrent to this study.
- Bleeding disorder independent of AML
- Patients with uncontrolled systemic fungal, bacterial, viral or other infection (defined as persistent disease signs/symptoms without improvement despite appropriate antibiotics or other treatment)
- HIV Infection
- Pregnant or lactating women
- Any significant concurrent disease, illness, psychiatric disorder or history of serious organ dysfunction that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
Diagnosis of another malignancy, unless the patient is disease-free for at least 3 years following the completion of curative intent therapy, with the following exceptions:
- Myelodysplastic syndrome (MDS) in patients with AML after MDS according to the WHO classification
- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
- Known hypersensitivity to any of the investigational medical products
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：なし
- 介入モデル：単一グループの割り当て
- 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：処理
|
Treatment is stratified according to patients age (< 60 years vs. ≥ 60 years). Medication: Patients < 60 years:
Patients ≥ 60 years:
Clofarabine will be given in escalating doses to cohorts of at least three patients: Clofarabine:
Patients will be recruited according to a 3+3 design. New cohorts will be initiated depending on toxicity of the previous cohort during the first induction cycle. Enrollment will begin with dose level 1. |
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 |
|---|---|---|
|
maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin
時間枠：six weeks
|
maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin in the therapy of previously untreated AML and high risk for induction failure
|
six weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
complete remission rate
時間枠：12 weeks
|
complete remission rate after two cycles of induction therapy
|
12 weeks
|
|
relapse-free, event-free and overall survival
時間枠：4 years
|
4 years
|
|
|
blast reduction in the bone marrow after the first induction cycle
時間枠：15 days
|
15 days
|
|
|
duration of aplasia
時間枠：12 weeks
|
12 weeks
|
|
|
therapy-associated morbidity and mortality
時間枠：12 weeks
|
12 weeks
|
|
|
course of molecular and cytogenetic markers during chemotherapy
時間枠：four years
|
molecular and cytogenetic markers will be evaluated by cytognetic analysis and molecular techniuques (e.g.
RT-PCR)
|
four years
|
|
fraction of patients who receive an allogeneic stem cell transplantation in first complete remission
時間枠：four years
|
four years
|
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：Juergen Krauter, MD、Hannover Medical School
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
2012年1月1日
一次修了 (予想される)
2013年4月1日
研究の完了 (予想される)
2015年9月1日
試験登録日
最初に提出
2012年2月14日
QC基準を満たした最初の提出物
2012年2月16日
最初の投稿 (見積もり)
2012年2月17日
学習記録の更新
投稿された最後の更新 (見積もり)
2012年2月20日
QC基準を満たした最後の更新が送信されました
2012年2月17日
最終確認日
2012年2月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- KS-2009-003
- 2010-021719-18 (EudraCT番号)
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。