Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Azacitidine

Decitabine

Ponatinib

Sorafenib

Quizartinib

Crenolanib

Antimetabolites

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Cohort #1: Participants with no previous leukemia therapy (including no previous FLT3 inhibitor therapy) for either: a) front-line treatment of elderly (age 65 and greater) FLT3-mutated AML patients, or b) patients unable or unwilling to receive standard intensive therapy.

Part 1: Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant continues on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Cohort #2: Participants with relapsed/refractory FLT3-mutated AML that have not received prior FLT3 inhibitor therapy.

Part 1: Participants receive Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant continues on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Cohort #3: Participants with relapsed/refractory FLT3-mutated AML, that have received previous FLT3 inhibitor therapy (including, but not limited to, quizartinib, crenolanib, sorafenib, other FLT3 inhibitors).

Part 1: Participants receive Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant will continue on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Part 1: Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle.

Part 2 Phase I Dose Escalation: 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

5-azacytidine

About 30 days after end-of-study visit, study staff calls participant and asks if they have had any side effects and/or started any new treatment(s).

If disease appears to be responding to study drugs, study staff calls participant every 3-6 months for up to 5 years and asks how they are doing and about any side effects they may be having.

Phone Calls

Naval Daver, MD

The goal of Part 1 of this clinical research study is to learn if ponatinib alone can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this drug will also be studied.

The goal of Part 2 of this clinical research study is to find the highest tolerable dose of ponatinib in combination with 5-azacytidine and to learn if the highest dose level found can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this combination will also be studied.

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to either Part 1 or Part 2 based on when they join this study.

If participant is enrolled in Part 1, they will receive ponatinib alone for the first cycle. If the doctor thinks it is needed, the dose level may be increased. If the disease does not respond to ponatinib alone, participant will continue on to Part 2 of this study.

Part 2 of this clinical research study will have 2 phases: Phase 1 (dose escalation) and Phase 2 (dose expansion).

In Part 2, participant will be assigned to a study group based on when they join this study. Up to 3 groups of 30 participants will be enrolled in Phase 1 of Part 2, and up to 60 participants will be enrolled in Phase 2.

If participant is enrolled in Phase 1, the dose of ponatinib they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of ponatinib. Each new group will receive a higher dose of ponatinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ponatinib is found.

If participant is enrolled in Phase 2, they will receive ponatinib at the highest dose that was tolerated in Phase 1.

All participants in Part 2 will receive the same dose level of 5-azacytidine.

Study Drug Administration:

Each study cycle is 28 days.

Participant will take ponatinib tablets by mouth 1 time every day while they are on study. Participant should swallow the tablets whole. Participant should not crush them.

If participant is enrolled in Part 2, they will receive 5-azacytidine either by vein over about 1 hour or as an injection under the skin on Days 1-7 of each study cycle or on Days 1-5, 8, and 9 of each study cycle (if the clinic is closed on a weekend).

If the doctor thinks it is needed, the dose level, dosing schedule, or study cycle may be changed and/or delayed. The study doctor will discuss any changes with participant.

Study Visits:

On Day 1 of each cycle (+/- 4 days), participant will have a physical exam.

On Day 1 (+/-1 day) of Cycles 1-3 and then every 3 cycles after that (Cycles 6, 9, 12, and so on), participant will have an EKG.

On Day 1 of Cycle 2 and then every 3 cycles after that, participant will have an ECHO or MUGA performed.

One (1) time each week during Cycles 1-3 and then 1 time every 2-4 weeks after that, blood (about 1 tablespoon) will be drawn for routine tests. Participant may be able to have these blood draws performed at a local lab or clinic that is closer to their home. The results of the testing will be sent to MD Anderson for review.

On Day 28 (+/- 7 days) of Cycles 1, 3, and then every 1-3 cycles after that, participant will have a bone marrow aspiration/biopsy to check the status of the disease.

One (1) time every 3 cycles, if participant can become pregnant, blood (about 1-2 tablespoons) will be drawn for a pregnancy test.

At any time while participant is on study, if the doctor thinks it is needed:

* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* Participant may have a bone marrow aspiration/biopsy to check the status of the disease.

Length of Study:

Participant will receive ponatinib alone or ponatinib and 5-azacytidine for as long as the doctor thinks it is in their best interest. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the follow-up visits.

End-of-Study Visit:

Within 14 days after participant's last dose of study drug(s):

* Participant will have a physical exam.
* Blood (about 2-3 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, participant will have a bone marrow aspirate/biopsy to check the status of the disease.

Follow-Up:

About 30 days after the end-of-study visit, a member of the study staff will call participant to ask if they have had any side effects and/or started any new treatment(s). This call should last about 5 minutes. If the study staff thinks it is needed, participant may also be asked to come into the clinic for a physical exam.

Long-Term Follow-Up:

If the disease appears to be responding to the study drugs, a member of the study staff will call participant every 3-6 months for up to 5 years to ask how they are doing and about any side effects they may be having. Each call should last about 5 minutes. Participant may also be asked to come into the clinic for a physical exam, if the study staff thinks it is needed.

This is an investigational study. 5-azacytidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Ponatinib is commercially available and FDA approved for the treatment of specific groups of chronic myeloid leukemia (CML) participants. Their use in this study is considered investigational. The study doctor can explain how the study drugs are designed to work.

Up to 132 participants will take part in this study. All will be enrolled at MD Anderson.

Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

Phase I/II, Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

MTD defined as highest dose level with \</= 1 out of 6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment. DLT defined as clinically significant non-hematologic adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications.

CRc defined as complete remission (CR), complete remission with incomplete platelet recovery (CRp), or complete remission with incomplete blood count recovery (CRi). Response defined by achievement of CRc at any point in time within the first 3 cycles of therapy, or prior to going off study, for those patients discontinuing treatment before completion of 3 cycles of therapy.

Ariad Pharmaceuticals

M.D. Anderson Cancer Center

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Anti-Infective Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Cytarabine

Dexamethasone

Methotrexate

Prednisone

Vincristine

Dexamethasone acetate

Imatinib Mesylate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

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.

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.

Imatinib

Study Director

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.

The drug being tested in this study is called ponatinib. Ponatinib is being tested to treat people who have newly diagnosed Ph+ ALL. This study will look at the efficacy of ponatinib in participants in addition to standard care.

The study will enroll approximately 230 participants. Participants will be randomized in a 2:1 ratio to receive oral ponatinib or imatinib (Cohort A and Cohort B, respectively) daily throughout the study.

All participants will be asked to take ponatinib or imatinib at the same time each day with reduced-intensity chemotherapy in induction phase (Cycles 1 to 3), consolidation phase (Cycles 4 to 9) and maintenance phase (Cycles 10 to 20). At the end of the 20 cycles, participants will remain on ponatinib or imatinib (administered as a single agent). The dose of ponatinib in consolidation and maintenance phase will start with the last dose given in the previous phase. The dose can be modified based on MRD-negative CR results.

This multi-center trial will be conducted in Argentina, Australia, Austria, Belarus, Brazil, Bulgaria, Canada, Chile, France, Mexico, Greece, Italy, Japan, Korea, Republic Of, Poland, Romania, Russia, Spain, Taiwan, Province Of China, Turkey, Finland and the United States. Participants including those who achieve a clinical response, may receive study drug until they are deceased, have failed to achieve the primary endpoint, have experienced relapse from CR or have progressive disease, have an unacceptable toxicity, have withdrawn consent, have proceeded to HSCT, or until the sponsor terminates the study, whichever occurs first. After disease progression, all participants will be contacted every 3 months for survival follow-up. Participants will be followed until completion of the study or until the participant's death has been reported.

It is an open-label trial, therefore investigators and participants are unblinded.

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 provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

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).

EFS is defined as the dates of randomization until death due to any cause or failure to achieve CR by end of induction or relapse from CR. 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) greater than (\>) 1000 per micro liter (/mcL) (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L).Relapse from CR: reappearance of blasts in the blood or BM (\>=5%) or in any extramedullary site after a CR.

CR is defined as meeting all the following for at least 4 weeks (that is, no recurrence): 1. No circulating blasts and \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.

Molecule response is assessed by 3-Log Reduction (MR3), Molecular Response 4-Log Reduction (MR4) and Molecular Response 4.5-Log Reduction (MR4.5). MR3 is defined as molecular response 3-log reduction (\<=0.1% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with \>=1000 ABL1 transcripts. MR4 is defined as molecular response 4-log reduction (\<=0.01% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with \>=10,000 ABL1 transcripts. MR4.5 is defined as Molecular response 4.5-log reduction (\<=0.0032% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with \>=32,000 ABL1 transcripts.

PIF is defined as participants who received treatment for ALL but never achieved CR or CRi by the end of induction. PIF is not limited by the number of unsuccessful treatments; this disease status only applies to recipients who have never been in CR or CRi. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.

ORR is defined as CR + CRi by end of induction. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L). CRi is defined as hematologic complete remission with incomplete hematologic recovery and meeting all criteria for CR except platelet count and/or ANC.

MRD is defined as the percentage of participants achieving CR who are MRD-negative at multiple intervals after end of induction. MRD negativity: \<=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in cDNA with \>=10,000 ABL1 transcripts. Relapse from CR: Reappearance of blasts in the blood or BM (\>=5%) or in any extramedullary site after a CR.

Duration of MRD-negative CR is defined as interval between the first assessment at which the criteria for MRD-negative CR are met until the earliest date at which loss of MRD negativity or relapse from CR occurs. MRD negativity (MR4): \<=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in cDNA with \>=10,000 ABL1 transcripts. CR is defined as meeting all the following for at least 4 weeks (that is, no recurrence): 1. No circulating blasts and \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L). Relapse from CR: Reappearance of blasts in the blood or BM (\>=5%) or in any extramedullary site after a CR.

Duration of CR is defined as interval between the first assessment at which the criteria for CR are met until the earliest date at which relapse from CR occurs. CR is defined as meeting all the following for at least 4 weeks (that is no recurrence): 1. No circulating blasts and \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L). Relapse from CR: Reappearance of blasts in the blood or BM (\>=5%) or in any extramedullary site after a CR.

Time to treatment failure is defined as time to end of study randomized treatment (except for hematopoietic stem cell transplantation \[HSCT\] without loss of MRD-negative CR) due to safety and efficacy reasons. MRD-negative CR is achieved when a participant meets the criteria for both MRD negativity and CR. MRD-negativity: \<=0.01% BCR-ABL1/ABL1, or undetectable BCR-ABL1 transcripts in 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 \<5% blasts in the BM. 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (CNS involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. ANC \>1000/mcL (or \>1.0\*10\^9/L). 5. Platelets \>100,000/mcL (or \>100\*10\^9/L).

Duration of MR4.5 is defined as interval between the first assessment at which the criteria for MR4.5 are met until the earliest date at which loss of MR4.5 occurs. MR4.5 is molecular response 4.5-log reduction (\<=0.0032% BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in cDNA with \>=32,000 ABL1 transcripts.

On-study participants with or without HSCT will be evaluated. OS is defined as interval between randomization and death due to any cause, censored at the last contact date when the participant was alive.

On-study participants with or without HSCT will be evaluated. Relapse from CR is defined as reappearance of blasts in the blood or BM (\>=5%) or in any extramedullary site after a CR.

OS is defined as interval between the randomization and death due to any cause, censored at the last contact date when the participant was alive.

Takeda

Safety population was defined as all participants who were randomized to the ponatinib or imatinib arm and received at least 1 dose of any study drug.

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 (IP) (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 (CP) 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 (MP) up to data cut-off date: 12 August 2022.

Cohort A: Ponatinib 30 mg

Cohort B: Imatinib 600 mg

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Hispanic or Latino

Non-Hispanic and Latino

Not reported

Unknown

Race/Ethnicity, Customized

Australia

China

Korea, South

Taiwan

Austria

France

Greece

Italy

Poland

Russia

Spain

Turkey

Canada

Mexico

United States

Argentina

Brazil

Region of Enrollment

Number analyzed are the number of participants available for height at baseline.

Height

Number analyzed are the number of participants available for weight at baseline.

Weight

Number analyzed are the number of participants available for BSA at baseline.

Body Surface Area (BSA)

ITT analysis set was defined as all participants who were randomized.

Medical

ITT population with p190/p210 variant was defined as all participants in the ITT population who were identified by the central laboratory as having baseline breakpoint cluster region-Abelson1 (BCR-ABL1) dominant variants of p190 or p210.

Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase

Event-free Survival (EFS)

Percentage of Participants With CR and Incomplete Complete Remission (CRi)

Percentage of Participants With Molecular Response

Percentage of Participants With Primary Induction Failure (PIF)

Percentage of Participants With Overall Response Rate (ORR)

Percentage of MRD-Negative CR

Duration of MRD-Negative CR

Duration of CR

Time to Treatment Failure

Duration of MR4.5

Percentage of On-Study Participants With Overall Survival (OS)

Percentage of On-Study Participants With Relapse From CR

Overall Survival (OS)

IP (Cycles 1-3) (Cycle Length=28 Days)

CP (Cycles 4-9) (Cycle Length=28 Days)

MP (Cycles 10-20) (Cycle Length=28 Days)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Blast Crisis

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

This is an observational registry to further characterize the safety profile of patients with chronic myeloid leukemia in the chronic phase (CP-CML), accelerated phase (AP-CML), blast phase (BP-CML), or Ph+ALL treated with Iclusig (ponatinib) in routine clinical practice in the US. The registry is focused on analysis of vascular occlusive events.

The registry is being conducted in an effort to better understand rates, risk factors, and outcomes associated with vascular occlusive events in patients treated with Iclusig (ponatinib) in real world settings. This registry study will collect information about patient demographics, leukemia diagnosis, previous anti-cancer treatments, history of cardiovascular disease, risk factors for vascular complications, and concurrent medications (including antiplatelet and/or anticoagulant agents).

An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®

A Postmarketing Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG® (Ponatinib) in Routine Clinical Practice in the United States (OMNI).

All VOEs will be entered into the EDC (Electronic Data Capture system)

Subject medical history and family medical history will be entered into the EDC

The category/type of outcome (e.g. Death, Disability/Permanent Damage, Hospitalization, Other), the time of duration, and status (continuing, resolved, fatal) will be entered into the EDC.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)	NCT02829840	Leukemia FLT3-Mutated Ac... FLT3-Mutated Hi...	Ponatinib 5-azacytidine Phone Calls	18 Years -	M.D. Anderson Cancer Center
A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia	NCT03589326	Philadelphia Ch...	Ponatinib Imatinib Vincristine Dexamethasone Cytarabine Methotrexate Prednisone	18 Years -	Takeda
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)	NCT02829840	Leukemia FLT3-Mutated Ac... FLT3-Mutated Hi...	Ponatinib 5-azacytidine Phone Calls	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for iclusig

Every month we try and update this database with for iclusig cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for iclusig

Every month we try and update this database with for iclusig cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for iclusig cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.