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Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia

Primary Purpose

AML

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Cytarabine
all-trans retinoic acid
Arsenic Trioxide
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AML

Eligibility Criteria

14 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age of 14 to 55 years old;
  2. Patients that meet the diagnostic criteria(WHO 2008 criteria) of AML (except APL subtypes) and with NPM1-mutated.
  3. Reached CR after induction regimen.
  4. ECOG score of ≤ 2;
  5. Patients with eligible laboratory examination including liver,renal and heart function.
  6. Adult patients are willing to participate in the study and sign the informed consent by themselves or by their immediate family. Patients under 18 years old willing to participate should have their legal guardians sign the informed consent.

Exclusion Criteria:

  1. Secondary leukemia.
  2. Patients had other tumor at active stage or had received radiotherapy or chemotherapy in the last 6 months due to other tumor.
  3. Patients with other blood diseases(for example, haemophiliacs) are excluded.However, patients with abnormal blood count, but with undiagnosed MDS or MPD patients are included.
  4. Acute panmyelosis with myelofibrosis and myeloid sarcoma patients;
  5. With BCR-ABL fusion gene;
  6. Pregnant or lactating women;
  7. With ineligible renal or liver function;
  8. With active cardiovascular disease;
  9. Severe infection disease including uncured tuberculosis pulmonary aspergillosis;
  10. AIDS;
  11. Patients had central nervous system involvement when they were diagnosed as AML.
  12. Patients with epilepsy or dementia or other mental disease who couldn't understand or follow the research.
  13. Drugs, medical, mental or social situation may distract patients from following the research or being evaluated the results.
  14. Patients with other factors which were considered unsuitable to participate in the study by the investigators.

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

High Dose of Cytarabine

HDAC + ATRA + ATO

Arm Description

Patients receive high dose of cytarabine.

Patients receive high dose of cytarabine plus ATRA and ATO treatment.

Outcomes

Primary Outcome Measures

Relapse-Free Survival Rate (RFS)
RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for NPM1 mutated leukemia patients who achieve CR.

Secondary Outcome Measures

Non-relapse Mortality
Overall Survival Rate (OS)
Cumulative incidence of relapse

Full Information

First Posted
January 12, 2017
Last Updated
March 19, 2020
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT03031249
Brief Title
Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia
Official Title
Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 8, 2017 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this open-label, randomized, prospective clinical trial, nucleophosmin-1(NPM1) mutated acute myeloid leukemia (AML) patients who have reached CR are randomized into two groups.The control group receive high-dose cytarabine(HDAC) regimen while the experimental group receive high dose of cytarabine plus tretinoin(ATRA) and arsenic trioxide(ATO) treatment.The safety and efficacy of ATRA and ATO is evaluated.
Detailed Description
In this open-label, randomized, prospective clinical trial, NPM1- mutated AML patients who have reached CR are randomized into two groups. In experimental group, patients receive cytarabine at a dose of 3g/㎡/d on the first, third and fifth day, ATRA at a dose of 30mg/㎡/d on day 1-14 and ATO at a dose of 0.15mg/kg/d (maximum, 10mg/d) on day 1-14. Patients in control group only receive high dose of cytarabine. The safety and efficacy of ATRA plus ATO regimen is evaluated.The primary outcome is relapse-free survival rate after treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High Dose of Cytarabine
Arm Type
Active Comparator
Arm Description
Patients receive high dose of cytarabine.
Arm Title
HDAC + ATRA + ATO
Arm Type
Experimental
Arm Description
Patients receive high dose of cytarabine plus ATRA and ATO treatment.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
HDAC
Intervention Description
Cytarabine at a dose of 3g/㎡/d on the first, third and fifth day.
Intervention Type
Drug
Intervention Name(s)
all-trans retinoic acid
Other Intervention Name(s)
ATRA
Intervention Description
ATRA at a dose of 30mg/㎡/d on day 1-14.
Intervention Type
Drug
Intervention Name(s)
Arsenic Trioxide
Other Intervention Name(s)
ATO
Intervention Description
ATO at a dose of 10mg/d on day 1-14
Primary Outcome Measure Information:
Title
Relapse-Free Survival Rate (RFS)
Description
RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for NPM1 mutated leukemia patients who achieve CR.
Time Frame
Within 5 years after randomization
Secondary Outcome Measure Information:
Title
Non-relapse Mortality
Time Frame
through treatment completion, an average of 5 months
Title
Overall Survival Rate (OS)
Time Frame
Within 5 years after randomization
Title
Cumulative incidence of relapse
Time Frame
Within 5 years after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age of 14 to 55 years old; Patients that meet the diagnostic criteria(WHO 2008 criteria) of AML (except APL subtypes) and with NPM1-mutated. Reached CR after induction regimen. ECOG score of ≤ 2; Patients with eligible laboratory examination including liver,renal and heart function. Adult patients are willing to participate in the study and sign the informed consent by themselves or by their immediate family. Patients under 18 years old willing to participate should have their legal guardians sign the informed consent. Exclusion Criteria: Secondary leukemia. Patients had other tumor at active stage or had received radiotherapy or chemotherapy in the last 6 months due to other tumor. Patients with other blood diseases(for example, haemophiliacs) are excluded.However, patients with abnormal blood count, but with undiagnosed MDS or MPD patients are included. Acute panmyelosis with myelofibrosis and myeloid sarcoma patients; With BCR-ABL fusion gene; Pregnant or lactating women; With ineligible renal or liver function; With active cardiovascular disease; Severe infection disease including uncured tuberculosis pulmonary aspergillosis; AIDS; Patients had central nervous system involvement when they were diagnosed as AML. Patients with epilepsy or dementia or other mental disease who couldn't understand or follow the research. Drugs, medical, mental or social situation may distract patients from following the research or being evaluated the results. Patients with other factors which were considered unsuitable to participate in the study by the investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lijun Liu
Phone
86-22-23909237
Email
bloodgcp@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
lijun Liu
Phone
86-22-23909237
Email
bloodgcp@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia

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