Imatinib for Sickle Cell Anemia

(IMPACT Trial)

Recruiting at 1 trial location

Overseen By Seethal Jacob, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Indiana University

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take certain CYP3A4 inducers 14 days before and during the study, and certain CYP3A4 inhibitors 7 days before and during the study. Check with the trial team about your specific medications.

What data supports the idea that Imatinib for Sickle Cell Anemia is an effective drug?

The available research shows that Imatinib is primarily used for treating chronic myeloid leukemia (CML) and not Sickle Cell Anemia. The studies focus on its effectiveness in CML, where it has shown significant results, such as inducing a complete response in about 60% of cases. However, there is no data provided that supports its effectiveness for Sickle Cell Anemia. ^{1 2 3 4 5}

What safety data exists for Imatinib in treating diseases?

Imatinib, also known as Imatinib Mesylate, Gleevec, Glivec, and other names, is generally well tolerated with a favorable safety profile. It is primarily used to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Common mild side effects include nausea, myalgia, edema, muscle cramps, and gastrointestinal symptoms. Severe adverse effects are rare, and most side effects occur early in treatment and are manageable. The safety profile allows for a high benefit-risk ratio, making it a preferred treatment option for CML and GIST. ^{2 6 7 8 9}

Is the drug Imatinib Mesylate a promising treatment for Sickle Cell Anemia?

Imatinib Mesylate is a drug that has shown promise in treating certain types of cancer, like chronic myeloid leukemia and gastrointestinal tumors, by targeting specific proteins involved in these diseases. However, there is no information in the provided research articles about its effectiveness for Sickle Cell Anemia. ^{1 2 10 11 12}

Eligibility Criteria

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.

Inclusion Criteria

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

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

My organs are functioning well.

Exclusion Criteria

I am taking other medications.

Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

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

Treatment Details

Interventions

• Imatinib Mesylate (Tyrosine Kinase Inhibitor)

Trial Overview 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.

Participant Groups

Group I: Imatinib Intervention Experimental Treatment 1 Intervention

Imatinib Mesylate is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Imatinib Mesylate for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia
• Gastrointestinal Stromal Tumor
• Hypereosinophilic Syndrome
• Dermatofibrosarcoma Protuberans
• Systemic Mastocytosis

Approved in Japan as Imatinib Mesylate for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia
• Gastrointestinal Stromal Tumor
• Hypereosinophilic Syndrome
• Dermatofibrosarcoma Protuberans
• Systemic Mastocytosis

Approved in China as Imatinib Mesylate for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia
• Gastrointestinal Stromal Tumor
• Hypereosinophilic Syndrome
• Dermatofibrosarcoma Protuberans
• Systemic Mastocytosis

Approved in Switzerland as Imatinib Mesylate for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia
• Gastrointestinal Stromal Tumor
• Hypereosinophilic Syndrome
• Dermatofibrosarcoma Protuberans
• Systemic Mastocytosis

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Purdue University

Collaborator

Trials

239

Recruited

72,200+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Findings from Research

Imatinib mesylate, a drug used to treat chronic myeloid leukemia, may be linked to ischemic maculopathy, which can lead to significant vision problems, as demonstrated in a case study of a 62-year-old woman.

The patient developed severe visual impairment and retinal abnormalities after starting imatinib therapy, highlighting the need for careful monitoring of patients for visual symptoms while on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular ischemia associated with imatinib mesylate therapy for chronic myeloid leukemia. Roth, DB., Akbari, S., Rothstein, A.[2014]

Imatinib mesylate (IM) is an effective first-line treatment for chronic myeloid leukemia (CML) that works by inhibiting the bcr-abl fusion protein, but it can cause mild side effects like nausea and muscle cramps.

In some patients, IM can lead to significant skin reactions, such as photoinduced dermatitis and oral lichenoid reactions, which may require discontinuation of the drug or treatment with steroids, highlighting the need for monitoring skin changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate. Brazzelli, V., Muzio, F., Manna, G., et al.[2017]

Imatinib mesylate (Glivec) is an effective targeted therapy for chronic myelogenous leukemia (CML), showing positive results in both newly diagnosed patients and those resistant to interferon, as well as in advanced phases of the disease.

The publication discusses mechanisms of resistance to imatinib and potential strategies to overcome this resistance, including dosage escalation and combination therapies with other treatments like immunotherapy and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate (STI 571)--a new oral target therapy for chronic myelogenous leukemia (CML). Chrobák, L., Voglová, J.[2016]

In a study of 94 adult patients with Philadelphia-positive chronic myeloid leukemia treated with imatinib, 63.6% developed monocytopenia, with anemia being the most common type of cytopenia observed.

Most cytopenias were of grade 2 or 3 severity, with anemia present at baseline and resolving within the first year, while neutropenia and thrombocytopenia developed within 12 months and resolved within 24-36 months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytopenia among CML Patients on Imatinib in Kenya: Types, Grades, and Time Course. McLigeyo, A., Rajab, J., Ezzi, M., et al.[2022]

In a study of 25 chronic-phase CML patients who had stable complete cytogenetic response after at least one year of treatment with imatinib mesylate, an 80% success rate was achieved in mobilizing and collecting autologous CD34+ cells for potential future use.

The mobilization of CD34+ cells was successful regardless of the duration of the disease or previous treatments, suggesting that this approach could be a viable option for patients who may develop resistance to imatinib and are not suitable for allogeneic transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral blood progenitor cell collection in chronic myeloid leukemia patients with complete cytogenetic response after treatment with imatinib mesylate. Perseghin, P., Gambacorti-Passerini, C., Tornaghi, L., et al.[2015]

Imatinib, a tyrosine kinase inhibitor, has significantly improved the prognosis for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST), showing high rates of cytogenetic and molecular responses across all phases of CML.

The drug is well tolerated, with only mild adverse effects such as joint pain and gastrointestinal symptoms, primarily occurring in the first two years of treatment, making it a safe and effective oral option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. Wolf, D., Rumpold, H.[2021]

BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for patients with chronic myeloid leukemia (CML), but their varying safety profiles allow for personalized treatment plans based on individual patient factors.

In managing adverse events (AEs) during TKI treatment, strategies such as dose adjustments, monitoring, and supportive care can help optimize patient outcomes and minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety review of tyrosine kinase inhibitors in chronic myeloid leukemia - What to look for when treatment-free remission is not an option. Lipton, JH., Brümmendorf, TH., Gambacorti-Passerini, C., et al.[2022]

Imatinib mesylate (Glivec) is the standard first-line treatment for chronic myeloid leukemia (CML) due to its high response rates and favorable safety profile, but switching to a copy version of the drug may lead to treatment failure, as seen in two case studies.

In one case, a patient relapsed after switching to the copy drug, while another patient experienced severe complications and died shortly after the switch, highlighting the need for caution and further research on the safety and efficacy of copy versions of imatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing therapy from Glivecto a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports. Asfour, IA., Elshazly, SA.[2023]

Imatinib mesylate (Gleevec) is a highly effective oral anticancer drug that specifically targets protein tyrosine kinases involved in chronic myeloid leukemia and gastrointestinal stromal tumors, showing remarkable clinical efficacy.

The treatment is generally well tolerated with a low risk of severe side effects, and most adverse effects, such as mild edema and nausea, are manageable without needing to stop therapy permanently.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications for imatinib mesylate therapy and clinical management. Guilhot, F.[2019]

In a study of 48 patients with various blood disorders, imatinib did not show significant clinical responses in those with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), atypical chronic myeloid leukemia (CML), or chronic myelomonocytic leukemia (CMML).

However, imatinib was well tolerated and showed some effectiveness in patients with myelofibrosis, where 71% of those with spleen enlargement experienced a significant reduction in spleen size, and preliminary results in polycythemia vera indicated a decrease in the need for phlebotomies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. Cortes, J., Giles, F., O'Brien, S., et al.[2015]

Two patients undergoing treatment with imatinib mesylate for metastatic gastrointestinal stromal tumor developed granulomatous diseases, highlighting a rare complication of this standard therapy.

Biopsy of enlarged lymph nodes is crucial for accurate diagnosis, as one patient was successfully treated for tuberculosis, while the other remained stable without treatment, indicating that careful monitoring can be safe in the absence of detectable infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tuberculous and non-tuberculous granulomatous lymphadenitis in patients receiving imatinib mesylate (glivec) for metastatic gastrointestinal stromal tumor. Agaimy, A., Brueckl, V., Schmidt, D., et al.[2021]

In a study of 6 children with chronic myelogenous leukemia (CML) treated with imatinib mesylate for a median of 78.5 months, growth velocity was initially suppressed but improved over time, indicating a potential long-term recovery in growth despite early treatment effects.

The study found that 33.3% of patients had decreased bone mineral density (BMD), which was associated with longer imatinib exposure, and highlighted a high prevalence of vitamin D insufficiency, suggesting that vitamin D supplementation could be beneficial for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of imatinib in children with chronic myelogenous leukemia. Choeyprasert, W., Yansomdet, T., Natesirinilkul, R., et al.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Macular ischemia associated with imatinib mesylate therapy for chronic myeloid leukemia. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate. [2017]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

Imatinib mesylate (STI 571)--a new oral target therapy for chronic myelogenous leukemia (CML). [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Cytopenia among CML Patients on Imatinib in Kenya: Types, Grades, and Time Course. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Peripheral blood progenitor cell collection in chronic myeloid leukemia patients with complete cytogenetic response after treatment with imatinib mesylate. [2015]

6. New Zealand pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Long-term safety review of tyrosine kinase inhibitors in chronic myeloid leukemia - What to look for when treatment-free remission is not an option. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Changing therapy from Glivecto a "copy" imatinib results in a worsening of chronic myeloid leukemia disease status: two case reports. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Indications for imatinib mesylate therapy and clinical management. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. [2015]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Tuberculous and non-tuberculous granulomatous lymphadenitis in patients receiving imatinib mesylate (glivec) for metastatic gastrointestinal stromal tumor. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Adverse effects of imatinib in children with chronic myelogenous leukemia. [2017]