What side effects are associated with this type of intervention?

Common treatments for Acute Leukemia, including Venetoclax (a Bcl-2 inhibitor), dasatinib, prednisone, rituximab, and blinatumomab, are associated with several side effects. Venetoclax can cause neutropenia, infections, and tumor lysis syndrome. Dasatinib may lead to fluid retention, pleural effusion, and myelosuppression. Prednisone, an anti-inflammatory drug, can result in hyperglycemia, increased infection risk, and osteoporosis. Rituximab can cause infusion-related reactions and infections. Blinatumomab is associated with cytokine release syndrome and neurotoxicity. These treatments, while effective, require careful monitoring for these adverse events.

What prior FDA approvals exist?

Venetoclax, a Bcl-2 inhibitor, has been studied and used in combination with other agents for the treatment of various types of leukemia, including Acute Myeloid Leukemia (AML) and Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (ALL). The FDA has approved azacitidine, a hypomethylating agent, for post-remission maintenance therapy of AML. Decitabine, another hypomethylating agent, is used for AML treatment and can be administered in both outpatient and inpatient settings. These drugs, often used in combination with Venetoclax, represent significant advancements in the treatment of acute leukemias.

What other types of research exist?

Promising novel alternatives to Venetoclax for acute leukemia patients include: <ol> <li>Blinatumomab: A bispecific T-cell engager (BiTE) antibody construct that targets CD19 on B cells and engages T cells to kill the cancer cells.</li> <li></li> </ol> Inotuzumab Ozogamicin: An antibody-drug conjugate targeting CD22, used particularly in B-cell precursor acute lymphoblastic leukemia (ALL). 3. Chimeric Antigen Receptor T-cell (CAR-T) Therapy: Specifically, tisagenlecleucel for B-cell precursor ALL, which involves modifying a patient's T cells to target and kill leukemia cells. 4. Dasatinib: A tyrosine kinase inhibitor used in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). 5. Combination Therapies: Regimens combining drugs like dasatinib, prednisone, rituximab, and blinatumomab are being studied for their efficacy in treating Ph+ ALL.

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Tyrosine Kinase Inhibitor

Combination Therapy for Acute Lymphoblastic Leukemia

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

The most common treatments for Acute Leukemia work by targeting specific mechanisms crucial for cancer cell survival and proliferation. Venetoclax, a Bcl-2 inhibitor, induces apoptosis by blocking the Bcl-2 protein. Cytarabine and anthracyclines like daunorubicin disrupt DNA synthesis and function, leading to cell death. Tyrosine kinase inhibitors such as dasatinib block enzymes essential for cancer cell growth, while monoclonal antibodies like rituximab target specific antigens on cancer cells, enhancing immune system response. These targeted approaches are crucial for effectively eliminating cancer cells and potentially reducing treatment-related toxicity.

Phase 1

Recruiting

Led By Jessica T Leonard

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

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

Must have

Must be able to take oral medication

Eastern Cooperative Oncology Group (ECOG) status =< 2

Must not have

Pregnant persons are excluded from this study because dasatinib is a pregnancy category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dasatinib, breastfeeding should be discontinued if the mother is treated with dasatinib. These potential risks may also apply to venetoclax for which the pregnancy category and risks to the fetus are unknown

Subjects with any gastrointestinal condition which would lead to inability to absorb an oral medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months

Awards & highlights

Summary

This trial tests a combination of five drugs to treat a specific type of aggressive leukemia. The drugs work together to stop cancer cell growth, reduce inflammation, and help the immune system target cancer cells. The trial aims to find the best dose and assess the safety and effectiveness of this treatment.

Who is the study for?

Adults with newly diagnosed or relapsed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) can join this trial. They must have good kidney function, no prior dasatinib treatment for relapsed cases, and be able to take oral medication. Pregnant or breastfeeding individuals, those with certain heart conditions, recent other cancer treatments, or active serious infections cannot participate.

What is being tested?

The trial is testing a combination of venetoclax with dasatinib, prednisone, and rituximab in patients. Venetoclax targets proteins that cancer cells need to survive; dasatinib blocks enzymes for cell growth; prednisone lowers immune response; rituximab may stop cancer spread.

What are the potential side effects?

Possible side effects include risk of infection due to lowered immunity from prednisone and rituximab. Venetoclax might cause digestive issues or fatigue. Dasatinib could lead to fluid retention and muscle pain. Each drug has its own profile of potential side effects.

Eligibility Criteria

Inclusion Criteria

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

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I can take pills by mouth.

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

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My kidneys work well, with a creatinine clearance of 50 mL/min or more.

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I have B-cell acute lymphoblastic leukemia with the Philadelphia chromosome.

Exclusion Criteria

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

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I am not pregnant or breastfeeding.

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I can take pills without issues absorbing them.

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I have a specific type of advanced leukemia.

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I have fluid buildup in the lining of my lungs or heart.

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I do not have any serious heart conditions like heart failure or irregular heartbeats.

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I have HIV, HBV, or HCV but am under effective treatment with an undetectable viral load.

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I have been diagnosed with a long QT syndrome.

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I am currently on antibiotics for a serious infection, not including treatment for neutropenic fever.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Incidence of dose-limiting toxicities

Secondary study objectives

Duration of complete molecular response (CMR)

Overall survival

Progression-free survival

Other study objectives

Cell viability percentage

Distribution of gene mutations

Frequency of BCR-ABL fusion protein subtypes

+2 more

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

Sepsis

11%

SARS-CoV-2 test positive

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (prednisone, dasatinib, venetoclax, rituximab)Experimental Treatment9 Interventions

See detailed description

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lumbar Puncture

2016

Completed Phase 3

~510

Biospecimen Collection

2004

Completed Phase 3

~2020

Blinatumomab

2014

Completed Phase 3

~1230

Bone Marrow Aspiration and Biopsy

2016

Completed Phase 1

~40

Dasatinib

2012

Completed Phase 3

~2320

Methotrexate

2019

Completed Phase 4

~4400

Prednisone

2014

Completed Phase 4

~2500

Rituximab

1999

Completed Phase 4

~2200

Venetoclax

2019

Completed Phase 3

~2200

0 / 12Eligibility 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 Leukemia work by targeting specific mechanisms crucial for cancer cell survival and proliferation. Venetoclax, a Bcl-2 inhibitor, induces apoptosis by blocking the Bcl-2 protein. Cytarabine and anthracyclines like daunorubicin disrupt DNA synthesis and function, leading to cell death. Tyrosine kinase inhibitors such as dasatinib block enzymes essential for cancer cell growth, while monoclonal antibodies like rituximab target specific antigens on cancer cells, enhancing immune system response. These targeted approaches are crucial for effectively eliminating cancer cells and potentially reducing treatment-related toxicity.

Synergistic effect of chidamide and venetoclax on apoptosis in acute myeloid leukemia cells and its mechanism.