Imatinib + Chemotherapy for Acute Lymphoblastic Leukemia

Not currently recruiting at 261 trial locations

Overseen By Mignon L. Loh

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must be taking: Imatinib

Must not be taking: Dasatinib, other TKIs

Disqualifiers: CML, Down syndrome, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for acute lymphoblastic leukemia (ALL) with a genetic change known as the Philadelphia chromosome. Researchers aim to determine if a different chemotherapy regimen combined with imatinib mesylate (a type of targeted therapy) can match the effectiveness of a stronger, more intense regimen but with fewer side effects. The trial also examines the effectiveness of this combination in ABL-class fusion positive ALL, a similar type of ALL. It seeks participants newly diagnosed with Philadelphia chromosome positive or ABL-class fusion positive ALL who have already begun initial treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that imatinib mesylate has been used safely in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). The FDA has approved it for this condition, indicating a good safety record. However, side effects can occur, especially when combined with chemotherapy.

Research shows that combining imatinib with strong chemotherapy can improve patient outcomes but also leads to more side effects. Common side effects include nausea, vomiting, and fatigue.

This trial tests whether a different, possibly less intense chemotherapy, when combined with imatinib, might cause fewer side effects while remaining effective. Safety is a major focus in all trials, and researchers closely monitor for any adverse events.

Prospective participants should discuss with the research team what side effects to expect and how they will be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute lymphoblastic leukemia, which typically involve a range of chemotherapy drugs, this new approach combines imatinib mesylate with specific chemotherapy protocols. Imatinib mesylate is unique because it targets the BCR-ABL protein, a culprit in certain leukemias, potentially enhancing the effectiveness of chemotherapy. Researchers are excited because this targeted action could lead to better outcomes and fewer side effects compared to traditional chemotherapy alone. Additionally, combining imatinib with multiple chemotherapy regimens (EsPhALL and COG/BFM) and the potential for hematopoietic stem cell transplantation (HSCT) offers a customized treatment pathway that could improve survival rates for patients with this aggressive cancer.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that imatinib mesylate, when combined with chemotherapy, effectively treats Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). In this trial, participants will receive imatinib mesylate with various chemotherapy regimens. One study using a specific chemotherapy plan called hyperCVAD found that all patients achieved complete remission, with no signs of cancer detected. Another study reported that 90% of patients reached complete remission when imatinib was paired with strong chemotherapy. These findings suggest that combining imatinib with chemotherapy significantly improves outcomes for individuals with Ph+ ALL. Additionally, imatinib is approved for treating several blood disorders, supporting its ability to target specific cancer cells effectively. ^{2 5 6 7 8}

Who Is on the Research Team?

Prof. Andrea Biondi

Principal Investigator

EsPhALL Network/ BFM Study Group

Lewis B Silverman

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled

My cancer has a confirmed ABL-class gene fusion.

Exclusion Criteria

Down syndrome

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol

I have a history of specific heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction IA Part 1

Patients receive induction IA according to standard of care on days 1-14

2 weeks

Induction IA Part 2

Patients receive imatinib mesylate and other chemotherapy agents

2.5 weeks

Induction IB

Patients receive imatinib mesylate and a combination of chemotherapy agents

5 weeks

Post-Induction Therapy

Patients receive various consolidation and intensification therapies based on risk classification

Varies by arm

Maintenance

Patients receive imatinib mesylate and other maintenance chemotherapy agents

Up to 104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Calaspargase Pegol
• Cyclophosphamide
• Daunorubicin Hydrochloride
• Dexamethasone
• Doxorubicin
• Etoposide
• Imatinib Mesylate
• Mercaptopurine
• Methotrexate
• Methylprednisolone
• Pegaspargase
• Prednisolone
• Therapeutic Hydrocortisone
• Thioguanine
• Vincristine Sulfate

Trial Overview

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.

How Is the Trial Designed?

Group I: Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Experimental Treatment 24 Interventions

See Detailed Description

Group II: Arm B (imatinib mesylate, COG/BFM chemotherapy) Experimental Treatment 18 Interventions

See Detailed Description.

Group III: Arm A (imatinib mesylate, EsPhALL chemotherapy) Experimental Treatment 23 Interventions

See Detailed Description

Calaspargase Pegol is already approved in United States, Canada for the following indications:

Approved in United States as Asparlas for:

• Acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged one month to 21 years

Approved in Canada as Asparlas for:

• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

EsPhALL network I-BFM Study Group

Collaborator

Trials

1

Recruited

480+

EsPhALL Network/ BFM Study Group

Collaborator

Trials

1

Recruited

480+

EsPhALL

Collaborator

Trials

2

Recruited

580+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4420214/

Final report of a phase II study of imatinib mesylate with hyper ...

In one of the first clinical trials combining imatinib with chemotherapy (the hyperCVAD regimen), we reported a complete remission rate of 100% in patients ...

2.

ashpublications.org

ashpublications.org/blood/article/100/6/1965/16459/A-phase-2-study-of-imatinib-in-patients-with

A phase 2 study of imatinib in patients with relapsed or ...

Imatinib therapy resulted in a clinically relevant hematologic response rate in relapsed or refractory Ph+ acute lymphoid leukemia patients, but development of ...

3.

mpnresearchfoundation.org

mpnresearchfoundation.org/news/gleevecr-approved-in-the-us-for-five-rare-life-threatening-disorders-with-limited-treatment-options/

GLEEVEC(R) APPROVED IN THE US FOR FIVE RARE ...

Gleevec has now been approved in the US for seven diseases, including two solid tumors and five blood disorders with molecular targets known to be inhibited by ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03007147

Study Details | NCT03007147 | Imatinib Mesylate and ...

This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with ...

5.

haematologica.org

haematologica.org/article/view/5482

Concurrent intensive chemotherapy and imatinib before ...

Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2016/021588s047lbl.pdf

GLEEVEC® (imatinib mesylate) tablets Label

1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL). 6.7 ... There is no pharmacokinetic or safety data on the concomitant use of Gleevec at doses ...

7.

mayoclinic.org

mayoclinic.org/drugs-supplements/imatinib-oral-route/description/drg-20068331

Imatinib (oral route) - Side effects & dosage

Safety and efficacy have not been established. ... For the treatment of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL):.

8.

ema.europa.eu

ema.europa.eu/en/documents/product-information/glivec-epar-product-information_en.pdf

Glivec, INN-imatinib - European Medicines Agency

Treatment schedule: On the basis of the existing data, Glivec has been shown to be effective and safe when administered at 600 mg/day in combination with ...