Table 2.

AML/CML PIP Decisions

Drug, PIP #	Clinical Studies	Until
Bosutinib EMEA-000727-PIP01-09	1. OL MC uncontrolled, DF study to evaluate PK, S and A of bosutinib in 10 to <18 years w/Ph+ CML in chronic phase resistant/intolerant to prior TKI therapy	DEC 2016
	2. Bioequivalence study with bosutinib in adults with paediatric age-appropriate formulation.
Decitabine EMEA-000555-PIP01-09-M04	1. OL MC multiple dose trial to evaluate PK, S and A of decitabine in sequential combination with cytarabine in children 1 month to <18 years with AML	JUL 2021
	2. OL, MC, R controlled trial to evaluate S and E of decitabine in sequential combination with cytarabine compared with standard of care induction therapy in children 1 month to <18 years with AML
Elacytarabine EMEA-001121-PIP01-10	1. OL, uncontrolled, dose-escalating trial to evaluate S, tolerability and PK of elacytarabine in patients 1 month to <18 years w/R/R acute leukaemia	SEP 2019
	2. OL externally controlled trial to evaluate S, A and E of elacytarabine in combination with liposomal daunorubicin compared to fludarabine, cytarabine and daunorubicin in patients 1 month to <18 years w/R/R AML with an initial DE stage to S of elacytarabine in combination with liposomal daunorubicin
Midostaurin EMEA-000780-PIP01-09-M01	1. OL DE, single-agent, MC, age-stratified trial to evaluate toxicity, PK, PD, S and A of midostaurin in 3 months to <18 years w/R/R ALL or AML	DEC 2019
	2. OL DE, randomized, active-controlled, age-stratified, MC trial to evaluate toxicity, PK, PD, S and A in children 3 months to <18 years with newly-diagnosed AML with certain FLT3 TKD mutation burden
	3. Pop PK/PD and outcome model to support extrapolation of E
Nilotinib EMEA-000290-PIP01-08-M03	1. Study to compare bioavailability of nilotinib when administered as intact capsule or the capsule content mixed with yogurt or apple sauce in adult volunteers	SEP 2015
	2. Multiple-dose OL single-agent, non-controlled trial to evaluate PK, PD, S and A in patients 1 to <18 years w/Ph+ CML in chronic or accelerated phase intolerant or resistant to imatinib- and/or dasatinib, or with R/R Ph+ ALL
	3. Multiple-dose OL single-agent, non-controlled, MC trial to evaluate PK, S and A in patients 1 to <18 years w/Ph+ CML in chronic or accelerated phase, intolerant or resistant to imatinib- or dasatinib or with newly diagnosed Ph+ CML in chronic phase
Ponatinib EMEA-001186-PIP01-11	1. OL, single-agent, DE, MC trial to investigate tolerability, S and A of ponatinib in children 1–17 years with malignant disease for which no effective treatment is known, and with an expansion cohort of children with chronic phase CML	DEC 2020
Volasertib EMEA-000674-PIP02-11	1. OL, non-controlled, DE trial to evaluate PK, PD, tolerability and toxicity of volasertib in patients 2 to <18 years w/acute leukaemia or advanced solid tumour, for whom no effective treatment is known	DEC 2023
	2. OL, DE trial to evaluate PK, PD, tolerability, toxicity, S and A of volasertib added to intensive CT in children
	3 months to <18 years with AML after failure of front-line intensive CT 3. OL, R, controlled trial to evaluate S and E of volasertib integrated with a standard intensive CT regimen in children 3 months to <18 years with AML after failure of the front-line intensive CT
Vosaroxin EMEA-001450-PIP01-13	1. OL, uncontrolled, MC, DE trial to evaluate tolerability, S, PK and A of vosaroxin in children with acute leukaemia 1 month to <18 years	JUL 2023
	2. OL, uncontrolled, MC trial to evaluate S and A of vosaroxin in combination with FLAG (fludarabine, cytarabine, filgrastim) in children 1 month to <18 years with a first relapse of AML

Abbreviations: OL, open label; PK, pharmacokinetics; PD, pharmacodynamics; DF, dose-finding; DE, dose escalating; w/, with; R/R, relapsed or refractory; BE, bioequivalence; Pop PK/PD, Population PK/PD; MC, multicenter; E, efficacy; S, safety; A, activity; R, randomized; AML, acute myeloid leukemia; ALL, acute lymphoblastic/lymphocytic/lymphoid leukemia; Ph+, Philadelphia positive; CT, chemotherapy; CML, chronic myeloid leukemia; PIP, pediatric investigation plan.