What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Disease (SCD) include hydroxyurea, NSAIDs, and blood transfusions. Hydroxyurea, the first-line therapy, can cause bone marrow suppression, leading to neutropenia and thrombocytopenia, and should be avoided during pregnancy. NSAIDs, while sometimes used for pain management, can lead to gastrointestinal, cardiovascular, and renal toxicities, particularly in patients with compromised kidney function. Blood transfusions, used for managing severe complications, carry risks of iron overload, alloimmunization, and transfusion reactions. Investigational therapies like imatinib mesylate, a tyrosine kinase inhibitor, are being studied for their potential to reduce vaso-occlusive crises, but their side effects in SCD patients are still under investigation.

What prior FDA approvals exist?

The FDA has approved several treatments for Sickle Cell Disease (SCD). Hydroxyurea is the most established treatment, recommended for reducing vaso-occlusive pain and other complications. It is approved for use in adults and children with SCD. Luspatercept, an erythroid maturation agent, is another FDA-approved drug for managing anemia in related conditions. While Imatinib Mesylate, a tyrosine kinase inhibitor, is being studied for its potential benefits in SCD, there are no current FDA-approved tyrosine kinase inhibitors specifically for SCD treatment.

What other types of research exist?

Promising novel alternatives to Imatinib Mesylate for Sickle Cell Disease patients include Hydroxyurea, which remains the first-line therapy due to its efficacy in reducing vaso-occlusive pain and other complications. Additionally, new medications that have become available and show promise include L-glutamine, voxelotor, and crizanlizumab. These therapies work through different mechanisms to reduce vaso-occlusive events and improve patient outcomes.

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Tyrosine Kinase Inhibitor

Imatinib for Sickle Cell Anemia (IMPACT Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Indiana University

Eligibility Criteria Checklist

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

Must have

a. Adequate bone marrow function defined as i. Peripheral absolute neutrophil count (ANC) ≥1000/µL ii. Platelet count ≥100,000/ µL (transfusion independent) b. Adequate renal function defined as i. Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 mL/min/1.73 m2 or ii. A serum creatinine based on age/gender c. Adequate Liver Function Defined As: i. Total bilirubin (sum of conjugated + unconjugated) ≤1.5 times upper limit of normal (ULN) for age, and ii. serum glutamate pyruvate transaminase (SGPT or ALT) <2.5 upper limit of normal. For the purpose of this study, the ULN for SGPT is 45 U/L iii. Serum albumin ≥2 g/dL d. Adequate cardiac function defined as: i. Shortening fraction or ejection fraction greater than the institutional norm, and ii. Corrected QT interval ≤450 msec

Performance Level: Karnofsky ≥80 for patients >10 years of age and Lansky ≥80 for patients ≤10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

Must not have

The following CYP3A4 inducers are prohibited 14 days before the start of imatinib and during the study with imatinib: rifampin, rifabutin, carbamazepine, Phenobarbital, phenytoin, St. John's wort, efavirenz, and tipranavir.

a. Patients currently on a chronic transfusion protocol are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up change from baseline band 3 phosphorylation at 7 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 20 Other Conditions

No Placebo-Only Group

Summary

This trial tests a pill used for other diseases on patients with sickle cell disease. The goal is to see if it can lower harmful proteins and particles in their blood. Researchers hope this will reduce pain crises and other complications over several months.

Who is the study for?

This trial is for individuals aged 18-25 with sickle cell disease who've had at least two vaso-occlusive pain episodes in the past year. They must have a certain level of organ function, no severe unrelated medical conditions, not be pregnant or breastfeeding, and agree to use contraception. Those on certain medications or with a history of other cancers or major surgery within two weeks are excluded.

What is being tested?

The trial tests Imatinib Mesylate's effects on sickle red blood cells by oral administration. It aims to reduce band 3 tyrosine phosphorylation levels and RBC-derived microparticles, potentially decreasing vaso-occlusive crises and acute chest syndrome over six months.

What are the potential side effects?

Possible side effects include digestive issues, liver problems, muscle cramps or pain, headache, dizziness, swelling around eyes or lower legs; difficulty breathing; weight gain; fatigue; nausea/vomiting; rash/skin reactions; anemia (low red blood cell count); infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I am mostly active and can carry out daily activities with little to no help.

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I have had at least 2 painful episodes in the last year due to blocked blood vessels that needed strong painkillers.

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I am between 18 and 25 years old.

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I have been diagnosed with sickle cell disease through specific blood tests.

Exclusion Criteria

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

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I have not taken any prohibited medications like rifampin or carbamazepine in the last 14 days.

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I am not on a long-term blood transfusion plan.

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I am currently not taking any other cancer treatments.

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I have a long-term liver condition like hepatitis or cirrhosis.

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I do not have severe heart problems like recent heart failure or heart attack.

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I do not have severe diseases like uncontrolled diabetes or infections.

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I do not have any infections that are currently uncontrolled.

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My family has a history of sudden cardiac death.

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I don't have a history of heart rhythm problems or need medications that affect heart rhythm.

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I am on a long-term blood transfusion plan.

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I have never taken Imatinib for my condition.

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I cannot take hydroxyurea because it lowers my blood cell counts too much.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ change from baseline band 3 phosphorylation at 7 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~change from baseline band 3 phosphorylation at 7 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and change from baseline band 3 phosphorylation at 7 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

Change in Functional RBC analysis

Changes in Biochemical Effects - Band 3 Phosphorylation

Changes in Biochemical Effects - Microparticle Release

Secondary study objectives

Acute Chest Syndrome (ACS)

Assessment toxicities of imatinib in patients with sickle cell anemia (SCA)

Hospitalizations

+2 more

Side effects data

From 2022 Phase 2 trial • 54 Patients • NCT03023046

26%

Febrile neutropenia

17%

Sepsis

Mucositis oral

Upper gastrointestinal hemorrhage

Hypotension

Hypertension

Intracranial hemorrhage

Enterocolitis

Peripheral motor neuropathy

Small intestinal obstruction

Lower gastrointestinal hemorrhage

Fungemia

Typhlitis

Oropharyngeal pain

Multi-organ failure

Abdominal pain

Hypoxia

Kidney infection

Edema limbs

Sinus bradycardia

Gastric hemorrhage

Myocardial infarction

Diarrhea

Fibrinogen decreased

Aspiration

Atrial fibrillation

Delirium

Endophthalmitis

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Chemotherapy)

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

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: Imatinib InterventionExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Imatinib

FDA approved

0 / 17Eligibility 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 Sickle Cell Disease (SCD) include hydroxyurea, voxelotor, and investigational therapies like imatinib mesylate. Hydroxyurea increases fetal hemoglobin (Hb F) levels, which reduces the polymerization of sickle hemoglobin (Hb S) and decreases vaso-occlusive events. Voxelotor works by keeping Hb S in its oxygenated form, preventing polymerization and subsequent sickling of red blood cells. Imatinib mesylate, a tyrosine kinase inhibitor, is being studied for its potential to reduce band 3 tyrosine phosphorylation and RBC-derived microparticles, which may decrease the frequency of vaso-occlusive crises. These treatments are crucial for SCD patients as they target the underlying mechanisms of the disease, reducing pain episodes, improving quality of life, and potentially preventing severe complications.

Advances in the management of sickle cell disease.