What side effects are associated with this type of intervention?

The most common treatments for Acute Lymphoblastic Leukemia (ALL) involving Tyrosine Kinase Inhibitors (TKIs) like Imatinib Mesylate are often combined with chemotherapy. Known side effects of TKIs include fatigue, nausea, diarrhea, muscle cramps, and skin rashes. When combined with chemotherapy, additional side effects can include myelosuppression (leading to anemia, neutropenia, and thrombocytopenia), increased risk of infections, hair loss, and gastrointestinal issues. Long-term use of these treatments may also lead to cardiotoxicity and liver dysfunction. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several Tyrosine Kinase Inhibitors (TKIs) for the treatment of Acute Lymphoblastic Leukemia (ALL), particularly for Philadelphia chromosome-positive (Ph+) ALL. Imatinib Mesylate was one of the first TKIs approved and has shown significant improvement in outcomes when combined with chemotherapy. Other TKIs such as Dasatinib have also been approved for similar indications, providing additional options for targeted therapy in Ph+ ALL patients.

What other types of research exist?

Promising alternatives to Imatinib Mesylate for ALL patients include Dasatinib and Ponatinib. Both are tyrosine kinase inhibitors that have shown efficacy in treating Philadelphia chromosome-positive ALL. Additionally, Venetoclax, a BCL2 inhibitor, combined with low-dose cytarabine, has shown promise in treating acute myeloid leukemia and related myeloid malignancies, which may be relevant for certain ALL cases.

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Chemotherapy

Imatinib + Chemotherapy for Acute Lymphoblastic Leukemia

Phase 3

Waitlist Available

Led By Prof. Andrea Biondi

Research Sponsored by Children's Oncology Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ph+ patients must have previously started Induction therapy with specific medications

ABL-class fusion patients must have definitive evidence of ABL-class fusions involving specific genes

Must not have

Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block

Prior treatment with dasatinib, or any TKI other than imatinib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial tests how well the drug imatinib works with different chemotherapy treatments for patients with specific types of leukemia. It aims to find out if a less intense chemotherapy regimen can be as effective as a stronger one but with fewer side effects. The study focuses on patients with certain types of acute lymphoblastic leukemia.

Who is the study for?

This trial is for patients up to 21 years old with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) or similar ABL-class fusion positive ALL. They must have started standard induction therapy but not received more than 14 days of it, and their organ functions should meet specific criteria. Excluded are those with chronic myelogenous leukemia, previous cancer treated with cytotoxic chemotherapy, uncontrolled infections or illnesses requiring intensive support, Down syndrome, pregnancy or breastfeeding women, and those unwilling to use contraception.

What is being tested?

The study tests imatinib mesylate combined with two different chemotherapy regimens in treating new cases of Philadelphia chromosome positive ALL. It aims to determine if a less intense chemo regimen can be as effective as a stronger one when paired with imatinib but cause fewer side effects. The effectiveness of this combination is also being tested on another group with ABL-class fusion positive ALL.

What are the potential side effects?

Potential side effects include reactions from the drug combination such as nausea, vomiting, hair loss, increased risk of infection due to lowered blood cell counts, heart problems like changes in rhythm or function; liver issues indicated by elevated bilirubin levels; kidney dysfunction; and general symptoms like fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I started treatment with specific drugs for my Ph+ condition.

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My cancer has a confirmed ABL-class gene fusion.

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I was diagnosed with ALL between the ages of 1 and 21.

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My cancer has a specific genetic change known as BCR-ABL1.

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My kidney function is normal or near normal.

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I have Ph+ condition and received less than 14 days of initial multiagent therapy.

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I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of specific heart rhythm problems.

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I have been treated with dasatinib or a TKI that is not imatinib.

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I do not have an ongoing serious infection or illness needing intense support.

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I am currently pregnant.

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My leukemia developed after treatment for another cancer.

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I have a history of chronic myelogenous leukemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Disease free survival (DFS) of Randomized Arms (standard risk [SR] Philadelphia chromosome [Ph+] acute lymphoblastic leukemia [ALL] patients)

Secondary study objectives

DFS on Randomized Arms (SR Ph+ ALL and ABL-class fusion positive patients)

EFS of all Ph+ patients

EFS of all eligibility ABL-class fusion positive ALL patients

+8 more

Other study objectives

Adherence to imatinib mesylate after allogeneic HSCT in high risk Ph+ ALL patients

Adherence to oral chemotherapeutic agents in standard risk Ph+ ALL patients

Frequency of p190 and p210 BCR-ABL1 fusion variants

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT)Experimental Treatment23 Interventions

See Detailed Description

Group II: Arm B (imatinib mesylate, COG/BFM chemotherapy)Experimental Treatment17 Interventions

See Detailed Description.

Group III: Arm A (imatinib mesylate, EsPhALL chemotherapy)Experimental Treatment22 Interventions

See Detailed Description

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Methotrexate

2019

Completed Phase 4

~4400

Doxorubicin

2012

Completed Phase 3

~8030

Cyclophosphamide

2010

Completed Phase 4

~2310

Allogeneic Hematopoietic Stem Cell Transplantation

2012

Completed Phase 2

~1240

Cytarabine

2016

Completed Phase 3

~3330

Dexamethasone

2007

Completed Phase 4

~2650

Dexrazoxane Hydrochloride

2013

Completed Phase 1

~50

Etoposide

2010

Completed Phase 3

~2960

Imatinib Mesylate

2003

Completed Phase 4

~800

Leucovorin Calcium

2011

Completed Phase 3

~12500

Methylprednisolone

2015

Completed Phase 4

~2280

Pegaspargase

2005

Completed Phase 3

~9260

Prednisolone

2005

Completed Phase 4

~3570

Therapeutic Hydrocortisone

2012

Completed Phase 3

~560

Vincristine Sulfate

2005

Completed Phase 3

~10270

Daunorubicin Hydrochloride

2011

Completed Phase 3

~5330

Mercaptopurine

2012

Completed Phase 4

~12550

Thioguanine

2012

Completed Phase 4

~10830

Filgrastim

2000

Completed Phase 3

~3690

Ifosfamide

2010

Completed Phase 4

~3140

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy, targeted therapy, and sometimes stem cell transplantation. Chemotherapy uses drugs to kill rapidly dividing cancer cells, while targeted therapies like Imatinib Mesylate (a Tyrosine Kinase Inhibitor) specifically inhibit the activity of proteins involved in cancer cell growth and survival, such as the BCR-ABL protein in Philadelphia chromosome-positive ALL. This targeted approach helps to minimize damage to normal cells and reduce side effects. These treatments are crucial for ALL patients as they aim to eradicate leukemic cells, achieve remission, and prevent relapse, thereby improving survival rates and quality of life.