NCT03589326|Active Not RecruitingPhase 3ResultsDMCFDA Drug

A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia

A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Takeda ClinicalTrials.gov

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5 other identifiers

Ponatinib-3001U1111-1206-2370HC6-24-c220300jRCT20312102302023-508463-71-00

Study Type

interventional

Target

245

Locations

19 countries

Sites

Timeline

RegisteredJul 2018

StartedOct 2018

CompletionJul 2027

Brief Summary

In this study, adults with newly-diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) will receive first-line therapy of ponatinib or imatinib. The main aim of this study is to compare the number of participants on each treatment that show no signs of disease. Participants will take tablets of either ponatinib or imatinib at the same time each day combined with reduced-intensity chemotherapy for up to 20 months. Then, they will continue with single-agent therapy (ponatinib or imatinib) until they meet the discontinuation criteria from the study.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

245

participants targeted

Target at P50-P75 for phase_3

Timeline

15mo left

Started Oct 2018

Longer than P75 for phase_3

Geographic Reach

19 countries

89 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.8 years study duration

Study Progress86%

Oct 2018Jul 2027

First Submitted

Initial submission to the registry

July 5, 2018

Completed

12 days until next milestone

First Posted

Study publicly available on registry

July 17, 2018

Completed

3 months until next milestone

Study Start

First participant enrolled

October 4, 2018

Completed

3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 12, 2022

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

October 27, 2023

Completed

3.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2027

Expected

Last Updated

November 26, 2025

Status Verified

November 1, 2025

Enrollment Period

3.9 years

First QC Date

July 5, 2018

Results QC Date

August 11, 2023

Last Update Submit

November 20, 2025

Conditions

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL)

Keywords

PonatinibImatinib mesylateBcr-Abl Tyrosine KinaseBcr-abl fusion proteinsIclusigGleevec

Outcome Measures

Primary Outcomes (1)

Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase
MRD-negative CR was achieved when a participant met the criteria for both MRD negativity and CR. MRD-negativity: ≤0.01 % breakpoint cluster region-Abelson (BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in complementary deoxyribonucleic acid (cDNA) with ≥ 10,000 ABL1 transcripts. CR: meeting all the following for at least 4 weeks (that is no recurrence):1. No circulating blasts and less than (\<) 5% blasts in the bone marrow (BM). 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (central nervous system \[CNS\] involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. Absolute neutrophil count (ANC) \> 1000 per microliter (/mcL) (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L).
From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)

Secondary Outcomes (13)

Event-free Survival (EFS)
Baseline up to approximately 3 to 6 years
Percentage of Participants With CR and Incomplete Complete Remission (CRi)
End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Percentage of Participants With Molecular Response
End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Percentage of Participants With Primary Induction Failure (PIF)
Up to 3 months
Percentage of Participants With Overall Response Rate (ORR)
Up to 3 months
+8 more secondary outcomes

Study Arms (2)

Cohort A: Ponatinib 30 milligram (mg)

EXPERIMENTAL

Ponatinib 30 mg, tablets, orally, once daily (QD), with vincristine 1.4 mg/m\^2 (max 2 mg) intravenous (IV), on Days 1 and 14 and dexamethasone 40 mg (\<60 years \[yrs\]) and 20 mg (≥60 yrs), orally, once on Days 1 to 4, Days 11 to 14 for up to 3 cycles (each cycle=28 days) in induction phase (reduced dose of ponatinib 15 mg upon achievement of MRD-negative CR at end of induction) followed by ponatinib last induction phase dose with cytarabine, 1000 mg/m\^2 as 2-hour IV infusion (\<60 yrs) and 250 mg/m\^2 (≥60 yrs) every 12 hours, IV on Days 1, 3, 5 of Cycles 2,4,6 and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (≥60 yrs), IV infusion, on Day 1 of cycles 1, 3, 5 in consolidation phase followed by ponatinib last consolidation phase dose with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Day 1 and prednisone 200 mg (\<60 yrs), 100 mg (≥60-69 yrs) and 50 mg(≥70 yrs) on Days 1 to 5 for up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.

Drug: PonatinibDrug: VincristineDrug: DexamethasoneDrug: CytarabineDrug: MethotrexateDrug: Prednisone

Cohort B: Imatinib 600 mg

ACTIVE COMPARATOR

Imatinib 600 mg, tablets, orally, QD, with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Days 1 and 14 and dexamethasone 40 mg (\<60 yrs) and 20 mg (≥60 yrs), orally, once on Days 1 to 4 and Days 11 to 14 in each 28-day cycle for up to 3 cycles in the induction phase followed by imatinib 600 mg, tablets, orally, QD, with cytarabine, 1000 mg/m\^2 every 12 hours as a 2-hour-IV infusion (\<60 yrs) and 250 mg/m\^2 every 12 hours (≥60 yrs), IV on Days 1, 3, and 5 of each 28-day even cycles (Cycles 2, 4, and 6), and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (≥60 yrs), IV infusion, on Day 1 of each 28-day odd cycles (Cycle 1, 3, and 5) in consolidation phase followed by imatinib 600 mg, tablets, orally, QD, along with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Day 1 and prednisone 200 mg (\<60 yrs), 100 mg (≥60-69 yrs) and 50 mg (≥70 yrs) on Days 1 through 5 in each 28-day cycle up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.

Drug: ImatinibDrug: VincristineDrug: DexamethasoneDrug: CytarabineDrug: MethotrexateDrug: Prednisone

Interventions

PonatinibDRUG

Ponatinib Tablets.

Also known as: Iclusig

Cohort A: Ponatinib 30 milligram (mg)

ImatinibDRUG

Imatinib Tablets.

Also known as: Gleevec

Cohort B: Imatinib 600 mg

VincristineDRUG

Vincristine IV injection.