What side effects are associated with this type of intervention?

Common treatments for Acute Lymphoblastic Leukemia (ALL), particularly those involving Tyrosine Kinase Inhibitors like Ponatinib, can cause side effects such as hypertension, skin rashes, abdominal pain, and pancreatitis. Chemotherapy agents used alongside TKIs often lead to myelosuppression, gastrointestinal symptoms (nausea, vomiting, diarrhea), and increased risk of infections. Long-term use of these treatments may also result in cardiotoxicity and hepatotoxicity.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Lymphoblastic Leukemia (ALL), particularly for Philadelphia chromosome-positive (Ph+) ALL, which include tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and ponatinib. These drugs target the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome abnormality. Additionally, blinatumomab, a bispecific T-cell engager (BiTE) antibody, has been approved for relapsed or refractory B-cell precursor ALL, offering another targeted treatment option.

What other types of research exist?

Promising alternatives to Ponatinib for treating Ph+ ALL include newer generation TKIs such as Acalabrutinib and Lorlatinib, which have shown efficacy in clinical trials. Additionally, combination therapies involving low-intensity chemotherapy with immunotherapy agents like Blinatumomab and targeted therapies such as Venetoclax are also being explored for their potential benefits.

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Monoclonal Antibodies

Chemotherapy + Ponatinib + Blinatumomab for Acute Lymphoblastic Leukemia

Q: What is the mechanism of action of this treatment?

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy, tyrosine kinase inhibitors (TKIs), and immunotherapy. Chemotherapy drugs, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, work by killing rapidly dividing cancer cells or stopping their division. TKIs like Ponatinib target specific enzymes (tyrosine kinases) involved in the growth and survival of leukemia cells, particularly in Philadelphia chromosome-positive ALL, by blocking the BCR-ABL protein. Immunotherapy, including agents like blinatumomab, harnesses the body's immune system to recognize and destroy cancer cells. These treatments are crucial for ALL patients as they aim to eradicate leukemia cells, achieve remission, and prevent relapse, thereby improving survival rates and quality of life.

Phase 2

Waitlist Available

Led By Elias Jabbour

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Patients >= 18 years of age with previously untreated Ph-positive ALL (either t(9;22) and/or BCR-ABL positive) including patients initiated on first cycle of hyper-CVAD before cytogenetics known

Patients >= 18 years of age with relapsed/refractory Ph-positive ALL or lymphoid accelerated or blast phase chronic myelogenous leukemia (CML)

Must not have

Active serious infection not controlled by oral or intravenous antibiotics

History of acute pancreatitis within 1 year of study or history of chronic pancreatitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of low-intensity chemotherapy, ponatinib, and blinatumomab in patients with a specific type of leukemia that has returned or is not responding to treatment. Chemotherapy stops cancer cell growth, ponatinib blocks enzymes needed by cancer cells, and blinatumomab helps the immune system fight cancer. Blinatumomab is an immunotherapy that has shown significant improvement in overall survival for patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. The goal is to see if this combination works better for these patients.

Who is the study for?

Adults with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia, either untreated or resistant to treatment. Participants must be in good physical condition (ECOG <=2), have normal liver and kidney function, agree to use effective contraception, and not have a history of significant heart disease or other serious medical conditions.

What is being tested?

The trial is testing the effectiveness of low-intensity chemotherapy combined with Ponatinib and Blinatumomab. It aims to see if this combination can stop cancer cells from growing by using different mechanisms including immune system modification.

What are the potential side effects?

Possible side effects include reactions related to the immune system, fatigue, digestive issues like nausea or diarrhea, blood cell count changes increasing infection risk, liver enzyme alterations, potential for allergic reactions, and infusion-related symptoms.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 or older with a specific type of leukemia (Ph-positive ALL) that hasn't been treated yet.

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I am 18 or older with a specific type of leukemia that has not responded to treatment.

Select...

I can do most of my daily activities on my own.

Exclusion Criteria

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

Select...

I have a serious infection that isn't getting better with antibiotics.

Select...

I have had pancreatitis within the last year or suffer from chronic pancreatitis.

Select...

I have or had an autoimmune disease that could affect my brain or spinal cord.

Select...

I have a bleeding disorder not related to my cancer.

Select...

I do not have another cancer that is expected to shorten my life to under a year.

Select...

I do not have severe heart failure.

Select...

I haven't taken strong CYP3A4 inhibitors recently.

Select...

I have very high triglyceride levels that aren't managed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 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

Complete molecular response (CMR) in newly diagnosed Philadelphia chromosome (Ph)-positive and/or BCR-ABL-positive participants

Overall response (OR) in participants with relapsed/refractory acute lymphoblastic leukemia

Secondary study objectives

CMR for relapsed/refractory population

Complete cytogenetic response

Event-free survival (EFS)

+2 more

Side effects data

From 2017 Phase 2 trial • 171 Patients • NCT01935336

67%

Grade 2 hypertension

67%

Grade 3 AE

100%

80%

60%

40%

20%

Study treatment Arm

Ponatinib SISH-/ISH+

Ponatinib SISH-/ISH-

Ponatinib SISH+/ISH+

Ponatinib SISH+/ISH-

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (chemotherapy, ponatinib, blinatumomab)Experimental Treatment9 Interventions

See Detailed Description.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Rituximab

1999

Completed Phase 4

~2990

Cytarabine

2016

Completed Phase 3

~3330

Pegfilgrastim

2013

Completed Phase 3

~4440

Blinatumomab

2014

Completed Phase 3

~1230

Cyclophosphamide

2010

Completed Phase 4

~2310

Filgrastim

2000

Completed Phase 3

~3690

Ponatinib

2015

Completed Phase 2

~830

Methotrexate

2019

Completed Phase 4

~4400

Vincristine

2003

Completed Phase 4

~2970

0 / 11Eligibility 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, tyrosine kinase inhibitors (TKIs), and immunotherapy. Chemotherapy drugs, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, work by killing rapidly dividing cancer cells or stopping their division. TKIs like Ponatinib target specific enzymes (tyrosine kinases) involved in the growth and survival of leukemia cells, particularly in Philadelphia chromosome-positive ALL, by blocking the BCR-ABL protein. Immunotherapy, including agents like blinatumomab, harnesses the body's immune system to recognize and destroy cancer cells. These treatments are crucial for ALL patients as they aim to eradicate leukemia cells, achieve remission, and prevent relapse, thereby improving survival rates and quality of life.