Imatinib for Pain in Sickle Cell Anemia

NCT03997903 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: IMPACT SCA
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

In this protocol, the investigators propose to evaluate the biochemical effects of imatinib on sickle red blood cells (RBCs). Patients will be administered imatinib mesylate orally following the guidelines previously established for use of imatinib in other disorders. The biochemical effects of imatinib on sickle RBCs will be examined, including changes in their levels of band 3 tyrosine phosphorylation and the abundances of RBC-derived microparticles in their blood. In addition, the patients will be monitored for symptoms of sickle cell disease (SCD). The investigators expect band 3 tyrosine phosphorylation to decrease dramatically in patients treated with imatinib. The investigators also anticipate a reduction in the numbers of RBC-derived microparticles in circulation (quantitated by assaying the number of glycophorin A positive microparticles in peripheral blood samples by flow cytometry. Most importantly, the investigators expect to see a reduction in the frequency of vaso-occlusive crises, and possibly acute chest syndrome and utilization of opioids. The study duration is planned as 6 months in order to provide adequate time for potential change in the primary endpoints (e.g. percent irreversibly sickled cells).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (4)

• Changes in Biochemical Effects - Band 3 Phosphorylation

  Percent change in Band 3 Phosphorylation tested in red blood cells. Band 3 is a protein found on the membrane of red blood cells.

  Change from baseline Band 3 Phosphorylation at 7 months

• Change in Amount of Microparticles Released From Red Blood Cells

  Change in Microparticles released from red blood cells. Microparticles are small vesicles released from red blood cells during aging, stress, or other types of damage that contain various proteins from inside the red blood cell, as well as from its membrane.

  change from baseline microparticle release at 7 months

• Change in Percent Irreversibly Sickled Cells

  Functional RBCs is analyzed by two components, one of which is percent irreversibly sickled cells. The percent of irreversibly sickled cells is measure by ektacytometry. Red blood cells that sickle and then cannot revert back to its normal shape are considered irreversibly sickled, increasing the likelihood of adhesion to vessel walls, as well as breakdown or hemolysis. Understanding the point of susceptibility of sickling helps us at what partial pressure of oxygen the red blood cell will sickle. The higher the partial pressure, the more resistant the red blood cell is to sickling/breakdown.

  Change from baseline of percent irreversibly sickled cells at 7 months

• Change in Point of Susceptibility to Sickling by OxygenScan

  Functional RBCs is analyzed by two components, one of which is Change in Point of Susceptibility to Sickling. This is measured by OxygenScan. The point of susceptibility of sickling shows at what partial pressure of oxygen (mmHg) the red blood cell will sickle. The higher the partial pressure, the more resistant the red blood cell is to sickling/breakdown.

  Change from baseline of point of susceptibility of sickling at 7 months

Secondary Outcomes (5)

• Number of Instances of Vaso-occlusive Crisis (VOC)

  Assessed monthly from treatment start up to 7 months

• Number of Instances of Acute Chest Syndrome (ACS)

  Assessed monthly from treatment start up to 7 months

• Opioid Use

  Assessed monthly from treatment start up to 7 months

• Number of Hospitalizations

  Assessed monthly from treatment start up to 7 months

• Assessment of Toxicities of Imatinib in Patients With Sickle Cell Anemia

  Assessed monthly from treatment start up to 7 months

Study Arms (1)

Imatinib Intervention

EXPERIMENTAL

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

The starting dose for subjects will be 340 mg/m2/day with a maximum dose of 600 mg daily. Patients will receive Imatinib orally once daily for 6 months.

Imatinib Intervention

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: patients must be ≥18 years of age and ≤25 years of age at the time of study entry.
• Diagnosis: Patients must have documented diagnosis of sickle cell disease (Hemoglobin SS Disease or S-Beta 0 Thalassemia) by either high pressure liquid chromatography (HPLC) or Hemoglobin Electrophoresis
• Disease status: Patients must have at least 2 documented episodes of vaso-occlusive pain in the prior year as defined by an acute episode of pain lasting greater than 24 hours, with no medically determined cause other than a vaso-occlusive event that resulted in treatment with oral or parenteral opiates or with a parenteral nonsteroidal anti-inflammatory drug.
• 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.
• Organ function requirements:
• 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
• Informed Consent: All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

You may not qualify if:

• Chronic transfusion protocol.
• a. Patients currently on a chronic transfusion protocol are not eligible
• Hydroxyurea Intolerance
• a. Patients who are ineligible for hydroxyurea due to persistent marrow suppression (e.g. thrombocytopenia, neutropenia)
• Pregnancy or Breast-Feeding
• a. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Concomitant Medications
• Investigational Drugs: Patients who are currently receiving another investigational drug.
• Anti-cancer agents: Patients who are currently receiving other anti-cancer agents.
• 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.
• The following CYP3A4 inhibitors are prohibited 7 days before the start of imatinib and during the study with imatinib: azole antifungals (itraconazole, ketoconazole); clarithromycin, erythromycin, diltiazem, verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfainavir); delavirdine.
• Patients who have an uncontrolled infection.
• Prior use of Imatinib: Patients who have previously received imatinib are not eligible for study.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
• Patient is \< 5 years free of a malignancy. Existence of any other malignant disease is not allowed.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: collaborator
• Indiana University: lead
• Purdue University: collaborator

Study Sites (2)

Riley Hospital for Children at IU Health

Indianapolis, Indiana, 46202, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Seethal Jacob, MD
• Organization: Indiana University

seejacob@iu.edu

317-944-8784

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: June 16, 2019
• First Posted: June 25, 2019
• Study Start: February 26, 2020
• Primary Completion: August 6, 2024
• Study Completion: August 6, 2024
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)