A study of volasertib combined with low-dose cytarabine versus investigator's choice as salvage therapy in patients with Acute Myeloid Leukemia

• Conditions: Relapsed or refractory acute myeloid leukemia in adult patients who are considered not to benefit from / not to be eligible for intensive salvage therapy and/or stem cell transplantation and have no established treatment options; MedDRA version: 13.1Level: LLTClassification code 10066638Term: Acute myeloid leukemia progressionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: LLTClassification code 10060558Term: Acute myeloid leukemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-023499-25-SE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-03
• Last Update Posted: 2 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1) Male or female adult with relapsed or refractory AML (except for acute promyelocytic leukemia, APL), considered not to benefit from / not to be eligible for standard intensive salvage therapy and / or stem cell transplantation based one of the following criteria:
a. AML patient = 60 years who fails to achieve complete remission after standard anthracycline-based induction or at least 2 cycles of non-anthracycline based induction
b. Relapsed AML patient = 60 years and at least one of the following:
•CR1 (first complete remission) < 18 months
•previous allogeneic stem cell transplant
•adverse genetic group •>1st relapse
c. AML patient <60 years who fails to achieve complete remission after at least 2 cycles of standard anthracycline-based induction or at least 1 cycle of high-dose cytarabine-based induction containing at least 6g/m2 of cytarabine
d. Relapsed AML patient <60 years who has already received high-dose cytarabine salvage (at least 6g/m2 of cytarabine) and/or allogeneic stem cell transplant

2)Signed and dated written informed consent by start date of Screening Visit in accordance with GCP and local legislation

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion Criteria

1) Previously untreated AML
2) Patient with Acute Promyelocytic Leukemia [AML subtype M3 according to the French-American-British (FAB) classification]
3) Hypersensitivity to one of the trial drugs or the excipients
4) Second malignancy currently requiring active therapy.
However, patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed.
5) Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator’s judgement is sufficient)
6) QTcF prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome, QTcF > 470 ms, etc.).
7) Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN), or AST or ALT > 5 x the ULN in case of known leukemia liver involvement
8) Prothrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)
9) Total Bilirubin > 1.5 mg/dL (> 26 µmol/L, SI unit equivalent) (unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis)
10) Serum creatinine > 2 mg/dL
11) Severe illness or organ dysfunction involving the heart, kidney, liver or other organ system (e.g. active infection, clinically relevant impairment of cardiac function, severe heart failure/cardiac insufficiency, unstable angina pectoris or history of recent myocardial infarction), which in the opinion of the investigator would interfere with the evaluation of the safety of the test drug or limit compliance with trial requirements
12) Any significant concurrent psychiatric disorder or social situation that according to the investigator’s judgement would compromise patient’s safety or compliance, interfere with consent, study participation, or interpretation of study results
13) Concomitant anti-leukemic treatment
14) Concomitant anti-infective therapy which, in the opinion of the investigator, is considered relevant for the evaluation of the efficacy or safety of the trial drug
15) Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate treatment)
16) Contraindications for cytarabine treatment according to the manufacturer’s product information provided in the ISF (applicable to patients randomized to Arm A)
17) Contraindications for the specific cytotoxic anti-leukemic product selected by the investigator according to the manufacturer’s product information (applicable to patients randomized to Arm B)
18) Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after study treatment
19) Pregnant or breast feeding patients
20) Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half times of the investigational drug before treatment with the present trial drug and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant
2

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified