IMatinib for PAin in Chronic Treatment of Sickle Cell Anemia (IMPACT SCA): A Pilot Study of Imatinib in Patients With Sickle Cell Anemia and Recurrent Vaso-occlusive Pain

About the study

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).

Study point of contact

Seethal Jacob, MD
317-944-8784
[email protected]

Locations

2 United States sites

Age

18 to 25 Years

Genotypes

Hemoglobin SS

Phase

Early Phase 1

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

participation requirements

1. Age: patients must be ≥18 years of age and ≤25 years of age at the time of study
entry.

2. 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

3. 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.

4. 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.

5. 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 6. 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.

participation restrictions

1. Chronic transfusion protocol.

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

2. Hydroxyurea Intolerance

a. Patients who are ineligible for hydroxyurea due to persistent marrow suppression
(e.g. thrombocytopenia, neutropenia)

3. 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.

4. Concomitant Medications

1. Investigational Drugs: Patients who are currently receiving another
investigational drug.

2. Anti-cancer agents: Patients who are currently receiving other anti-cancer
agents.

3. 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.

4. 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.

5. Patients who have an uncontrolled infection.

6. Prior use of Imatinib: Patients who have previously received imatinib are not eligible
for study.

7. Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study.

8. Patient is < 5 years free of a malignancy. Existence of any other malignant disease is not allowed. 9. 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). 10. 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. 11. Patients with a family history of sudden cardiac death. 12. 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). 13. Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis). 14. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. 15. Patient had a major surgery within 2 weeks prior to study entry.

Locations

  • Indianapolis, Indiana, United States, Riley Hospital for Children at IU Health, 46202 [Recruiting]
  • Cincinnati, Ohio, United States, Cincinnati Children's Hospital, 45229 [Recruiting]
Last updated 2021-10-04