Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ponatinib (Iclusig®) : Tyrosine Kinase Inhibitor (BCR-ABL); oral (tablets) : 30mg/day during 6 months (induction phase); Takeda \& Incyte Biosciences.

Imatinib (either Glivec® or any generic form) : Tyrosine Kinase Inhibitor (BCR-ABL, ABL, KIT and PDGFRA receptor tyrosine kinases); oral : 400 mg/day during at least 30 months (then, depending of MR4.5)

30mg/day; 6 months. Dose adaptation procedures are planned in case of toxicity.

400 mg/day; at least 30 months (M7 to M36), then depending of MR4.5 . Dose adaptation procedures are planned in case of toxicity.

Imatinib

Franck-Emmanuel NICOLINI, MD

The investigators hypothesize that, in newly diagnosed de novo chronic phase CML patients, an induction treatment with ponatinib for 6 months should increase the rate of patients reaching a stable MR4.5 allowing cessation of imatinib treatment.

The investigators proposal is to conduct a multicenter, Phase II trial to evaluate the safety, clinical and biological activity of an induction treatment with ponatinib for 6 months, followed by a consolidation treatment with imatinib in newly diagnosed de novo chronic phase CML patients.

TREATMENT PLAN :

All eligible patients will be treated:

* During the induction Phase (Month 1 to Month 6) with ponatinib (30mg/day) single agent; then
* During the consolidation Phase (Month 7 to Month 36) with imatinib (400mg/day) single agent; then
* From M36 :

  * Patients with stable MR4.5 (i.e. since at least 2 years) will enter in the TFR phase and will stop imatinib treatment. Thereafter, in case of MMR loss, imatinib will be re-introduced as per investigator judgement (including for dose).
  * Patients without stable MR4.5 will continue imatinib treatment until stable MR4.5, or M60, PD, death, withdrawal of consent or overall trial completion. Such patients will be allowed to enter into the TFR phase as soon as a stable 2-year MR4.5 is reached: however, they will be considered as a failure for the primary endpoint analysis.

STATISTICS :

A total of 170 patients will be enrolled in this study.

According to a Fleming design, with a P0=20% as minimal efficacy rate and P1=30% as an expected target, 156 patients should be enrolled, assuming an unilateral type I error alpha of 5% and 90% power. At the time of analysis, if at least 40 successes are observed among the 156 evaluable patients, the treatment will be considered as interesting for further investigation in this indication. Considering that some patients may withdraw their consent before 36 months (about 10%), the investigators plan to enrol 170 patients in total.

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

Safety and Efficacy of Ponatinib Followed by Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase

A Multicentre, Open-label Phase II Trial Evaluating the Safety and Efficacy of Ponatinib Induction Followed by Imatinib Maintenance in Adult Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) ≤ 65 Years

Rate of patients reaching a stable MR4.5 (BCR-ABL (IS) ≤0.0032% with at least 32,000 copies of ABL) for ≥ 2 years at Month 36 after initiation of ponatinib.

For all patients : Rate of patients with MR4.5; MR4.0 and MMR at 1, 2, 3, 6, 9, 12, 24 months after ponatinib initiation

For all patients : Rate of patients with a BCR-ABL/ABL (IS) ≤ 10% and rate of patients with CCyR (or its molecular equivalent, BCR-ABL/ABL (IS) ≤ 10%) at 3 and 6 months after ponatinib initiation.

For all patients : Time to MR4.5, MR4.0 or MMR following ponatinib initiation

For all patients : Duration of MR4.5, MR4.0 or MMR

For all patients : Progression Free survival

For patients reaching TFR criteria and following imatinib cessation: Rate of successful TFR (patients sill with MR4.5) at 3, 6, 9, 12 and 24 months after imatinib cessation

For patients reaching TFR criteria and following imatinib cessation: Duration of TFR after imatinib cessation.

For patients reaching TFR criteria and following imatinib cessation: OS after imatinib cessation

For patients reaching TFR criteria and following imatinib cessation: PFS after imatinib cessation

For patients reaching TFR criteria and following imatinib cessation: Event-free survival according ELN recommendations

For patients reaching TFR criteria and following imatinib cessation: Rate of TKI-withdrawal syndrome after Imatinib cessation

For patients reaching TFR criteria and following imatinib cessation: Rate of MMR, MR4.0 and MR4.5 recovery in case of imatinib re-introduction (

* Hematologic and non-hematologic AEs graded according to the NCI CTCAE v5.0
* Incidence of arterial thrombotic events during the induction phase and during the consolidation phase.

Evolution of Quality of life according to QLQ-CML24 questionnaire.

Evolution of Quality of life according to QLQ-C30 questionnaire.

Plasma concentrations of ponatinib over the 6 months of the induction period.

Compliance to ponatinib and imatinib as evaluated using the Morisky medication adherence scale questionnaire

Centre Leon Berard

Lonafarnib

SCH66336

Jorge Cortes, MD

The goal of this research is to see if giving the drug SCH66336 by mouth can improve the disease in patients with chronic or accelerated phase CML. The safety of this treatment will also be studied.

Objectives for this study are two-fold:

1. To determine the efficacy of SCH66336 in patients with chronic phase and accelerated phase CML in relation to response rate, duration of response, and survival.
2. To assess the toxicity of SCH66366 in these patients.

Phase II Study of SCH66336, A Farnesyltransferase Inhibitor in Chronic Myelogenous Leukemia (CML)

M.D. Anderson Cancer Center

Blast Crisis

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Participants initially received STI571 capsules or tablets, orally, initially once daily (400 mg) or (600 mg). The dosage was escalated from 400 mg to 600 mg and from 600 mg to 800 mg, on an individual basis as per the investigator's judgement. Treatment continued until death, or the development of intolerable toxicity, or the participant was considered not to benefit from treatment, whichever came first.

imatinib mesylate

Novartis Pharmaceuticals

This extension II study allowed for further follow-up of the disease under treatment with imatinib mesylate and allow the participants to continue to receive imatinib mesylate.

An Extension Study of the Safety and Anti-leukemic Effects of Imatinib Mesylate in Participants With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Blast Crisis

An Extension to a Phase II Open-label Study to Determine the Safety and Anti-leukemic Effects of STI571 in Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Myeloid Blast Crisis

Overall survival was defined as the number of events of death, expressed as a percentage, from the start of treatment to death, due to any reason.

Overall survival was defined as the time between start of treatment and death due to any reason. Overall survival for the participants was calculated by Kaplan-Meier estimates per month. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up.

After 31 July 2002 no safety data was collected in the clinical database and serious adverse events (SAEs) were reported in the safety database. No drug-related SAEs leading to discontinuation or drug-related deaths were reported after 31 July 2002 in the safety database.

Imatinib Mesylate (STI571)

Age, Continuous

Sex: Female, Male

The Intent-to-treat (ITT) population included all participants who enrolled in the study.

Study Director

Overall Survival

12 Months

24 Months

36 Months

48 Months

60 Months

72 Months

84 Months

96 Months

108 Months

120 Months

132 Months

144 Months

156 Months

Overall Survival (by Month)

Participants initially received STI571 capsules or tablets, orally, initially once daily (400 mg) or (600 mg). The dosage was escalated from 400 mg to 600 mg and from 600 mg to 800 mg on an individual basis as per the investigator's judgement. Treatment continued until death, or the development of intolerable toxicity, or the participant was considered not to benefit from treatment, whichever came first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Ponatinib Followed by Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase	NCT04070443	Philadelphia Ch... BCR-ABL Positiv...	Ponatinib Imatinib	18 Years - 65 Years	Centre Leon Berard
Phase II Study of SCH66336, A Farnesyltransferase Inhibitor in Chronic Myelogenous Leukemia (CML)	NCT00038597	Myelogenous Leu...	SCH66336	16 Years -	M.D. Anderson Cancer Center
Safety and Efficacy of Ponatinib Followed by Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase	NCT04070443	Philadelphia Ch... BCR-ABL Positiv...	Ponatinib Imatinib	18 Years - 65 Years	Centre Leon Berard
An Extension Study of the Safety and Anti-leukemic Effects of Imatinib Mesylate in Participants With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Blast Crisis	NCT00171158	Philadelphia Ch...	imatinib mesyla...	18 Years -	Novartis
An Extension Study of the Safety and Anti-leukemic Effects of Imatinib Mesylate in Participants With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Blast Crisis	NCT00171158	Philadelphia Ch...	imatinib mesyla...	18 Years -	Novartis

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