Imatinib for Pain in Sickle Cell Anemia (IMPACT)

  • STATUS
    Recruiting
  • End date
    Sep 11, 2023
  • participants needed
    20
  • sponsor
    Indiana University
Updated on 4 October 2022
opioid
opiates
absolute neutrophil count
electrophoresis
acute chest syndrome
chest syndrome
thalassemia
Accepts healthy volunteers

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).

Details
Condition Sickle Cell Disease
Treatment Imatinib Mesylate
Clinical Study IdentifierNCT03997903
SponsorIndiana University
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
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

Exclusion Criteria

Chronic transfusion protocol
Patients currently on a chronic transfusion protocol are not eligible
Hydroxyurea Intolerance
Patients who are ineligible for hydroxyurea due to persistent marrow suppression (e.g. thrombocytopenia, neutropenia)
Pregnancy or Breast-Feeding
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
Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
Patients with a history of QT prolongation, need for concomitant use of anti-arrhythmics or other agents known to prolong QT interval, or electrolyte derangement that cannot be corrected to within normal limits prior to initiation of study drug
Patients with a family history of sudden cardiac death
Patient has a severe and/or uncontrolled medical disease other than sickle cell disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis)
Patient has a known diagnosis of human immunodeficiency virus (HIV) infection
Patient had a major surgery within 2 weeks prior to study entry
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