Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine

NCT ID: NCT00995332

Last Updated: 2015-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2013-06-30

Brief Summary

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Hypothesis: Combined treatment with valproic acid and ATRA can be used to achieve disease stabilization for a subset of patients with acute myelogenous leukemia (AML), and this effect can be improved without serious toxicity by adding low-dose cytarabine to this treatment.

Adult patients \>18 years of age who can be included:

Elderly patients who cannot achieve standard chemotherapy, patients with relapsed or resistant AML.

Treatment: Combined therapy with:

Valproic acid, continuous therapy until disease progression ATRA, oral therapy for 14 days every three months Low-dose cytarabine 10 mg/m2 up to 10 injections during week 2 and 3, repeated every 3 months.

Detailed Description

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Patients to be included:

1. Elderly patients (\>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML).
2. Adult patients of any age (\>18 years of age) with relapsed or resistant AML who cannot receive conventional therapy.

Treatment:

Valproic acid to be started on day 1 as continuous therapy until disease progression.

ATRA administered from day 8 orally as 22.5 mg/m2 twice daily for 14 days, repeated every third month.

Low-dose cytarabine 10 mg/m2 from day 14 and continued as daily injections for up to 10 days, repeated every third month.

Supportive therapy is given according to the hospitals general guidelines.

Followup: The first 2 days treatment in hospital, later regular out-patient treatment. Controls will include clinical examination, peripheral blood parameters (including serum valproic acid levels), bone marrow samples.

Conditions

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Acute Myelogenous Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ATRA+valproc acid+low-dose cytarabine

Group Type EXPERIMENTAL

Cytarabine, all-trans retinoic acid, valproic acid

Intervention Type DRUG

ATRA: 22.5 mg/m2 twice daily for 2 weeks every third month Valproic acid: continuous therapy, dosage guided by serum levels Cytarabine: 10 mg/m2 once daily for up to 10 days every third month

Interventions

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Cytarabine, all-trans retinoic acid, valproic acid

ATRA: 22.5 mg/m2 twice daily for 2 weeks every third month Valproic acid: continuous therapy, dosage guided by serum levels Cytarabine: 10 mg/m2 once daily for up to 10 days every third month

Intervention Type DRUG

Other Intervention Names

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No other names

Eligibility Criteria

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Inclusion Criteria

* Recently diagnosed AML in patients unfit for intensive chemotherapy
* Patients with relapsed or refractory AML

Exclusion Criteria

* No informed consent
* Intolerance to study drugs
* Serious liver disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bergen

OTHER

Sponsor Role lead

Responsible Party

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Øystein Bruserud

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Oystein Bruserud, MD

Role: STUDY_CHAIR

University of Bergen, Norway

Locations

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Haukeland University Hospital and University of Bergen

Bergen, , Norway

Site Status

Countries

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Norway

References

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Fredly H, Ersvaer E, Kittang AO, Tsykunova G, Gjertsen BT, Bruserud O. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin Epigenetics. 2013 Aug 1;5(1):13. doi: 10.1186/1868-7083-5-13.

Reference Type BACKGROUND
PMID: 23915396 (View on PubMed)

Haaland I, Hjelle SM, Reikvam H, Sulen A, Ryningen A, McCormack E, Bruserud O, Gjertsen BT. p53 Protein Isoform Profiles in AML: Correlation with Distinct Differentiation Stages and Response to Epigenetic Differentiation Therapy. Cells. 2021 Apr 7;10(4):833. doi: 10.3390/cells10040833.

Reference Type DERIVED
PMID: 33917201 (View on PubMed)

Reikvam H, Hovland R, Forthun RB, Erdal S, Gjertsen BT, Fredly H, Bruserud O. Disease-stabilizing treatment based on all-trans retinoic acid and valproic acid in acute myeloid leukemia - identification of responders by gene expression profiling of pretreatment leukemic cells. BMC Cancer. 2017 Sep 6;17(1):630. doi: 10.1186/s12885-017-3620-y.

Reference Type DERIVED
PMID: 28877686 (View on PubMed)

Other Identifiers

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Rek VEST 231-06

Identifier Type: -

Identifier Source: org_study_id

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