Leukemia
Conditions
Keywords
ara-c, As2O3, pediatric, acute
Brief summary
Several groups, especially the PETHEMA group (in their LPA96 and 99 trials), obtained low relapse rates in newly diagnosed Acute Promyelocytic Leukemia (APL) patients by combining ll-transretinoic acid (ATRA) and anthracyclines without Ara-C, suggesting that avoiding Ara-C in the chemotherapy of APL reduced treatment toxicity without increasing relapses. While the relapse rate for the children with white blood cell(WBC) counts greater than 10×109/L at presentation were higher than those WBC counts less than 10×109/L (31% and 3.5%,respectively) in the LPA96 and 99 trials. A recent adult randomized trial show that avoiding Ara-C leads to an increased risk of relapse in the APL patients with WBC counts less than 10×109/L. The role of the Ara-C remains controversial. And there are very limited data reported on children with APL so far.
Detailed description
Some studies suggest patients with high-risk disease should be treated with intensified doses of anthracycline, or intermediate/ high-dose Ara-C or As2O3 as an early consolidation, so as to decrease the risk of relapse.However, a higher cumulative dose of anthracycline may lead to cardiac toxicity, especially for children. In addition, containing Ara-C will led to more therapy-related toxicity. The benefit to add Ara-C to the schedules is questionable and remains a matter of investigation in children.
Interventions
DRUGDNR:
DNR：45mg/m2 d1-3
DRUGAra-c
DNR+ARA-C：DNR：45mg/m2 d1-3;Ara-C :1g/m2 d1-3
Sponsors
Xiaofan Zhu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Acute Promyelocytic Leukemia (APL)
Exclusion criteria
* \> 14
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | two years | We assessed the OS of APL patients when ATRA and ATO were used. The overall survival (OS) durations was calculated from the date of diagnosis to last follow-up or death. |
| the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | 2 years | We assessed the EFS of APL patients treated with retinoic acid receptor alpha (ATRA) and Arsenic Trioxide (ATO) based trial. Event-free survival (EFS) was defined as time from diagnosis to last follow-up or an event (relapse or death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Side Effects | three years | Also, we compared the side effect and outcome between the two groups.To assessed whether Ara-C could be omitted when ATO and ATRA were used. |
Countries
China
Participant flow
Recruitment details
Eligible patients were those who were less than 14 years old, were newly diagnosed with APL, and had not previously received chemotherapy. Sixty-five patients were included in the study.
Pre-assignment details
The demonstration of PML-RARA transcripts, was required for inclusion in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| DNR+Ara-c one group treated with DNR+Ara-C | 30 |
| DNR（ no Ara-C) one group treated with DNR | 35 |
| Total | 65 |
Baseline characteristics
| Characteristic | DNR（ no Ara-C) | DNR+Ara-c | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 35 Participants | 30 Participants | 65 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 7 years | 8 years | 8 years |
| Haemoglobin | 81.0 g/L | 78 g/L | 78 g/L |
| Platelet count | 32.0 cells x 10^9/L | 24.5 cells x 10^9/L | 30.5 cells x 10^9/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants | 30 Participants | 65 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 35 participants | 30 participants | 65 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 22 Participants | 20 Participants | 42 Participants |
| white blood cell count | 5.47 cells x 10^9/L | 4.23 cells x 10^9/L | 4.71 cells x 10^9/L |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 65 | 0 / 65 | 0 / 65 | 0 / 65 | 0 / 35 | 0 / 30 | 0 / 65 |
| other Total, other adverse events | 0 / 65 | 55 / 65 | 21 / 65 | 3 / 65 | 0 / 65 | 0 / 35 | 0 / 30 | 0 / 65 |
| serious Total, serious adverse events | 12 / 65 | 2 / 65 | 1 / 65 | 0 / 65 | 0 / 65 | 0 / 35 | 0 / 30 | 0 / 65 |
Outcome results
Primary
the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial
We assessed the EFS of APL patients treated with retinoic acid receptor alpha (ATRA) and Arsenic Trioxide (ATO) based trial. Event-free survival (EFS) was defined as time from diagnosis to last follow-up or an event (relapse or death).
Time frame: 2 years
Population: There were 65 patients included in our study, including 35 in the DNR group and 30 in the DNR+Ara-C group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DNR Group | the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | relapse | 0 participants |
| DNR Group | the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | die | 0 participants |
| DNR+Ara-C Group | the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | relapse | 1 participants |
| DNR+Ara-C Group | the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | die | 0 participants |
Primary
the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial
We assessed the OS of APL patients when ATRA and ATO were used. The overall survival (OS) durations was calculated from the date of diagnosis to last follow-up or death.
Time frame: two years
Population: There were 65 patients included in our study, including 35 in the DNR group and 30 in the DNR+Ara-C group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DNR Group | the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | relapse | 1 participants |
| DNR Group | the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | died | 0 participants |
| DNR+Ara-C Group | the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | relapse | 0 participants |
| DNR+Ara-C Group | the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | died | 0 participants |
Comparison: The characteristics of all of the included patients were summarized using cross-tabulations (for categorical variables) and quantiles. Nonparametric tests were used to analyse comparisons between groups .EFS、disease-free survival (DFS) and OS were estimated using the Kaplan -Meier method, and log-rank tests were used. All P values were two-sided, and those with values of 0.05 or less were considered to be statistically significant.p-value: <0.05Log Rank
Secondary
Number of Participants With Side Effects
Also, we compared the side effect and outcome between the two groups.To assessed whether Ara-C could be omitted when ATO and ATRA were used.
Time frame: three years
Population: There were 66 patients included in our study. One patient gave up treatment due to the economic reasons. Then the number of the patients were 65, including 35 in the DNR group and 30 in the DNR+Ara-C group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DNR Group | Number of Participants With Side Effects | sepsis | 5 Participants |
| DNR Group | Number of Participants With Side Effects | platelet transfusion | 26 Participants |
| DNR Group | Number of Participants With Side Effects | red blood cell transfusion | 7 Participants |
| DNR Group | Number of Participants With Side Effects | relapse | 0 Participants |
| DNR+Ara-C Group | Number of Participants With Side Effects | platelet transfusion | 0 Participants |
| DNR+Ara-C Group | Number of Participants With Side Effects | relapse | 1 Participants |
| DNR+Ara-C Group | Number of Participants With Side Effects | sepsis | 1 Participants |
| DNR+Ara-C Group | Number of Participants With Side Effects | red blood cell transfusion | 7 Participants |