Simplified Patient Care Strategy in Decreasing Early Death in Patients With Acute Promyelocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
This clinical trial studies how well simplified patient care strategy works in decreasing early death in patients with acute promyelocytic leukemia. Implementing simplified acute promyelocytic leukemia guidelines along with support from acute promyelocytic leukemia experts may decrease deaths and improve survival.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate if the proposed patient care strategy, that includes use of simplified guidelines along with acute promyelocytic leukemia (APL) expert support, decreases the one-month induction mortality rate from 30% to under 15%. SECONDARY OBJECTIVES: I. To assess the overall survival 1 year after accrual is completed. II. To assess incidence and severity of differentiation syndrome. III. To correlate outcomes with time to initiation of all-trans retinoic acid (ATRA) from diagnosis or suspicion of diagnosis. IV. To compare outcomes between academic and community centers separately. V. To evaluate factors associated with outcome. OUTLINE: Patients receive standard of care treatment for APL. Patients? doctors regularly discuss with an APL expert to identify and mange treatment. After diagnosis, patients are followed up for 1 year.

Official Title
-----------------
A Simplified Patient Care Strategy to Decrease Early Deaths in Acute Promyelocytic Leukemia (APL)

Conditions
-----------------
Acute Promyelocytic Leukemia With PML-RARA, t(15;17)

Intervention / Treatment
-----------------
* Other: Best Practice
* Other: Laboratory Biomarker Analysis
* Procedure: Supportive Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed to have a diagnosis of APL, which is defined as: Positive t(15:17) by fluorescence in situ hybridization (FISH) or conventional karyotype Positive promyelocytic leukemia/retinoic acid receptor PML/RAR alpha by polymerase chain reaction (PCR) Patients must accept treatment and supportive care guidelines Referrals must be made as early as possible but no later than 5 calendar days after ATRA therapy is initiated; consent can be obtained up till day 7 or earlier Co-management can be started as soon as referral is made including weekends; the physician at the outlying facility should make every effort to call the APL expert at the first suspicion of APL

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (simplified guidelines and support)<br>Patients receive standard of care treatment for APL. Patients? doctors regularly discuss with an APL expert to identify and mange treatment. | Other: Best Practice<br>* Discussion between doctors and APL expert<br>* Other names: standard therapy;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Supportive Care<br>* Receive simplified guidelines and support<br>* Other names: Therapy, Supportive;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | Will be estimated by dividing total number of deaths within one month of study entry by total number of cases with at least one-month follow up data. 95% repeated confidence interval will be provided. | At 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance with treatment guidelines | Will be assessed as binary outcome and the successful compliance rate will be described with 95% confidence interval. A regression model will be developed to evaluate the factors associated with outcome. Data items such as age, risk status, comorbidity will be collected and evaluated. | Up to 1 year | 
| Length of hospital stay | Will be associated with toxicity measures. Will be dichotomized as ?mild? versus (vs.) ?severe? and the length of hospital stay will be compared using the two-sample t-test. | Up to 1 year | 
| Mortality rate | Will be compared between patients with long time or short time from diagnosis to treatment using the Fisher?s exact test. Will also be compared between lead institutions and outlying centers. | At 1 month | 
| Overall survival | Will be compared between the lead institutions and outlying centers and two-sided p-values will be reported. | At 1 month | 
| Overall survival (OS) | Will be described using the method of Kaplan-Meier. The median OS and one-year OS rate will be estimated and 95% confidence interval (CI) will be provided. | At 1 year | 
| Severity and duration of coagulopathy, bleeding, infections, and differentiation syndrome | Will be measured based on the Common Terminology Criteria for Adverse Events version 4.0. Analysis of the safety data will be mostly descriptive. The proportion of patients with the worst degree toxicity of grade 3 or higher will be assessed and presented with 95% CI. | Up to 1 year | 
| Time from diagnosis and initiation of treatment | Will be assessed and dichotomized as ?short? vs. ?long? using the median value. | Up to 1 year |