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RESEARCH QUESTION

Main research question:

Does digital droplet PCR (ddPCR) negativity for BCR-ABL1 predict a high (60% or higher) Treatment Free Remission (TFR) success rate in patients with a short (3-6 year) Tyrosine Kinase Inhbitor (TKI) treatment duration?

 

A secondary research question is if three novel tests correlate with TFR success rate, which may improve the predictive power of ddPCR testing:

a. Circulating residual CD26+CD34+ leukemic cells

b. Circulating CD56+ NK cells

c. Pneumococcal vaccine response

 

HYPOTHESES

I CML patients treated for 3-6 years with TKI and a negative ddPCR for BCR-ABL1 have a minimal TFR success rate of 60%, thus comparable to the general success rate of patients treated >6 years

II TFR success rate is higher in patients discontinuing TKI therapy who have

a. lower levels of CD26+CD34+ leukemic cells

b. higher levels of CD56+ NK cells

c. a positive pneumococcal vaccine response

 

STUDY DESIGN

Observational cohort study

 

STUDY POPULATION

Patients eligible for attempted TFR discontinuation (chronic phase CML, no previous switch in TKI for treatment failure, minimal 3 years total TKI therapy, durable deep molecular remission defined as MR 4.0 or better)

 

INTERVENTION

TKI cessation in CML patients treated for 3-6 years with a TKI who are ddPCR negative for BCR-ABL1

 

OUTCOME MEASURES

Sustained MMR (BCR-ABL <0,1% IS) at 12 months after TKI discontinuation

 

SAMPLE SIZE/DATA-ANALYSIS

For main study: calculated sample size of n=148

For substudy: estimated sample size of n=60

 

1. Main data analysis: Non-inferiority to a level of minimally 60% of proportion of sustained TFR at 12 months in patients with TKI treatment duration <6 years and with negative ddPCR BCR-ABL1 test.

2. Exploratory correlative analysis for three predictive factors: CD26+ leukemic cells and CD56+ NK cells as continuous variables; pneumococcal vaccine response as dichotomized and categorical variable; all vs. sustained MMR at 12 months after TKI discontinuation.

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