Trial Outcomes & Findings for Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia (NCT NCT02339740)

Last Updated: 2024-11-07

Results Overview

EFS is defined as the time from on study to failure to achieve hematological complete response (CR) prior to start of consolidation, persistence of molecular positive disease after minimal residual disease (MRD) positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

158 participants

Primary outcome timeframe

Up to 24 months

Results posted on

2024-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	Standard Risk WBC \<10,000 cells/µL	High Risk WBC ≥10,000 cells/µL
Overall Study STARTED	101	57
Overall Study COMPLETED	92	53
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Risk WBC \<10,000 cells/µL	High Risk WBC ≥10,000 cells/µL
Overall Study Death	1	0
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	5	1
Overall Study Inevaluable-RQPCR positive not confirmed	3	1

Baseline Characteristics

Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Risk n=101 Participants WBC \<10,000 cells/µL	High Risk n=57 Participants WBC ≥10,000 cells/µL	Total n=158 Participants Total of all reporting groups
Age, Categorical <=18 years	85 Participants n=5 Participants	53 Participants n=7 Participants	138 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	4 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	13.9 Years STANDARD_DEVIATION 4.5 • n=5 Participants	12.3 Years STANDARD_DEVIATION 4.7 • n=7 Participants	13.4 Years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	25 Participants n=7 Participants	73 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	32 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	14 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	37 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	34 Participants n=7 Participants	94 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	7 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	90 participants n=5 Participants	54 participants n=7 Participants	144 participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Australia	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: Patients ineligible, did not start treatment, or RQPCR positive not confirmed are excluded from analyses of EFS

Outcome measures

Outcome measures
Measure	Standard Risk n=98 Participants WBC \<10,000 cells/µL
Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients	97.9 percentage of participants Interval 93.4 to 99.3

PRIMARY outcome

Timeframe: Up to 24 months

Population: Patients ineligible, did not start treatment, or RQPCR positive not confirmed are excluded from analyses of EFS

EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits.

Outcome measures

Outcome measures
Measure	Standard Risk n=56 Participants WBC \<10,000 cells/µL
EFS in High Risk APL Patients	96.1 percentage of participants Interval 88.2 to 98.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 70 days

A Fisher's exact test will be used to compare the induction death rate for patients with FLT3 mutations to patients with wild type FLT3.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 70 days

For patients in remission at the end of induction, the log-rank test will be used to test for differences in DFS for those with end of induction real-time quantitative polymerase chain reaction (RQ-PCR) of \< 1 normalized copy number (NCN) compared with those with end of Induction RQ-PCR \>= 1 NCN.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 29 days of induction therapy

Will calculate the International Society of Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score and compare the sensitivity and specificity of ISTH with that of thrombomodulin using McNemar's test for paired data. To improve the predictive ability of the ISTH DIC score, will use a stepwise combination of biomarkers. Receiver operating characteristic (ROC) curve will be used to assess the accuracy in prediction of bleeding events during induction and the areas under the ROC curve will be compared.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of induction up to 2 years post-treatment

Actual CogState scores for each domain at each time point will be summarized and examined by descriptive statistics and scatter plots. Change in score for a domain from end of induction will be calculated and summarized by descriptive statistics. The mean change of score from end of induction to a later time-point will be estimated with its 95% confidence interval. Linear mixed models using scores from all time-points as outcome will also be used to estimate the change in scores between time-points with adjustment for within-patient correlation of the score by random effects for individual patients.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of induction up to 2 years post-treatment

Measured by the Behavioral Regulation, Working Memory and Metacognition Indices of the Behavior Rating Inventory of Executive Function. Change in score for a domain from end of induction will be calculated and summarized by descriptive statistics. The mean change of score from end of induction to a later time-point will be estimated with its 95% confidence interval. Linear mixed models using scores from all time-points as outcome will be used to estimate change in scores between time-points with adjustment for within-patient correlation of the score by random effects for individual patients.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years post-treatment

One sample t-test on the change of score will be used to examine if there is significant decline in neurocognitive function from end of induction to 2 years off therapy. Linear mixed models using scores from all time-points as outcome will also be used to estimate the change in scores between time-points with adjustment for within-patient correlation of the score by random effects for individual patients.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years post-treatment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years post-treatment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years post-treatment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years off-therapy

Psychosocial functioning over time as defined by declines on the Behavior Assessment System for Children-Second Edition (BASC-2) Anxiety, Depression, and Social Skills scores, and the Pediatric Quality of Life Inventory (PedsQL) Total and Physical Health scores.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment to 4 years

QOL over time as defined as declines on the BASC-2 Anxiety, Depression, and Social Skills scores, and the PedsQL Total and Physical Health scores.

Outcome measures

Outcome data not reported

Adverse Events

Standard Risk

Serious events: 3 serious events

Other events: 89 other events

Deaths: 1 deaths

High Risk

Serious events: 2 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard Risk n=101 participants at risk WBC \<10,000 cells/µL	High Risk n=57 participants at risk WBC ≥10,000 cells/µL
General disorders Death NOS	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
General disorders Multi-organ failure	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Infections and infestations Infections and infestations - Other, specify	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Nervous system disorders Depressed level of consciousness	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Nervous system disorders Encephalopathy	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Nervous system disorders Intracranial hemorrhage	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Nervous system disorders Seizure	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Psychiatric disorders Psychosis	0.00% 0/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	1.8% 1/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Respiratory, thoracic and mediastinal disorders Retinoic acid syndrome	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	1.8% 1/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Skin and subcutaneous tissue disorders Hypohidrosis	0.99% 1/101 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.	0.00% 0/57 • While patients were on protocol therapy (including up to 6 courses) or during follow-up. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior approval.
Publication restrictions are in place

Restriction type: OTHER