A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral tosedostat to standard induction therapy in AML and RAEB ≥ 66 years and very poor risk AML ≥ 18 years.

A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral tosedostat to standard induction therapy in AML and RAEB ≥ 66 years and very poor risk AML ≥ 18 years

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON22002

Enrollment

200

Registered

2010-08-23

Start date

2010-08-16

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid leukemia (AML), RAEB

Interventions

1. Arm A: Cycle I: Dauno/Cytarabine, cycle II: Cytarabine

2. Arm C: Cycle I: Dauno/Cytarabine/Tosedostat, cycle II: Cytarabine/Tosedostat.

Eligibility

Inclusion criteria

Inclusion criteria: 1. Patients eligible for standard chemotherapy; 2. Patients ≥ 66 years with a cytopathologically confirmed diagnosis according WHO classification of: A. AML (not APL) (see appendix A1), or; B. Refractory anemia with excess of blasts (RAEB) with an IPSS score ≥ 1.5. OR 3. Patients of any age ≥ 18 years with a cytopathologically confirmed diagnosis according WHO classification of very poor risk AML; 4. Subjects with secondary AML progressing from antecedent (at least 4 months duration) myelodysplasia are also eligible; 5. SGOT (AST) and SGPT (ALT) ≤ 1.5 x the upper limit of the normal range (ULN) at the laboratory where the analyses were performed; 6. Total serum bilirubin level ≤ 1.5 x the ULN at the laboratory where the analysis was performed; 7. Serum creatinine concentration ≤ 1.5 x ULN at the laboratory where the analysis was performed; 8. WHO performance status ≤ 2; 9. Written informed consent; 10. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment; 11. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion criteria

Exclusion criteria: 1. Acute promyelocytic leukemia; 2. Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period (< 2 weeks) with Hydroxyurea is allowed; 3. Past or current history (within the last 2 years prior to randomization) of malignancies except for the indication under this study and curatively treated: A. Basal and squamous cell carcinoma of the skin; B. In situ carcinoma of the cervix. 4. Blast crisis of chronic myeloid leukemia; 5. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months prior to randomization), myocardial infarction (≤ 6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure; 6. Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance; 7. Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study; 8. Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent; 9. Pregnant or lactating patients; 10. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.

Design outcomes

Primary

Measure	Time frame
Part A of the study: 1. To assess the safety and tolerability of tosedostat added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) and select the feasible dose level for part B of the study; 2. To assess in a randomized comparison the effect of tosedostat on the CR rate. Part B of the study: 1. To assess the safety and tolerability of tosedostat added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of tosedostat; 2. To assess in a randomized comparison the effect of the in Part A selected dose of tosedostat on the CR rate.	—

Measure

Time frame

Part A of the study: 1. To assess the safety and tolerability of tosedostat added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) and select the feasible dose level for part B of the study; 2. To assess in a randomized comparison the effect of tosedostat on the CR rate. Part B of the study: 1. To assess the safety and tolerability of tosedostat added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia) as regards the selected dose level of tosedostat; 2. To assess in a randomized comparison the effect of the in Part A selected dose of tosedostat on the CR rate.

—

Secondary

Measure	Time frame
For part B: 1. To determine the efficacy profile (event free survival (EFS), disease free survival (DFS) and overall survival (OS)) associated with the two therapy regimens; 2. To measure MRD by immunophenotyping in relation to clinical response parameters; 3. To identify potential biomarkers predictive of response, EFS, DFS and OS by exploratory genomic analysis (microarray, gene mutations).	—

Contacts

Public ContactG.J. Ossenkoppele

VUMC, Afd. Hematologie Postbus 7057

g.ossenkoppele@vumc.nl+31 20 4442604

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)

A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral tosedostat to standard induction therapy in AML and RAEB &#8805; 66 years and very poor risk AML &#8805; 18 years.