Imatinib for Sickle Cell Anemia

(IMPACT Trial)

No longer recruiting at 1 trial location

Overseen By Seethal Jacob, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Indiana University

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Chronic transfusion, Hydroxyurea intolerance, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of the drug imatinib (also known as Imatinib Mesylate) on sickle cell disease, a condition that causes painful episodes due to misshapen red blood cells. Researchers aim to determine if imatinib can reduce these painful episodes and improve blood health by altering certain blood cell properties. The trial seeks participants with sickle cell disease who have experienced at least two painful episodes in the past year. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage treatment development.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that patients usually tolerate imatinib mesylate well. Common mild side effects include nausea, muscle pain, swelling, muscle cramps, and stomach issues. Serious side effects are rare. Studies have found that imatinib can significantly reduce chronic pain in sickle cell anemia without causing major changes in blood. The FDA has already approved imatinib for other uses, so its safety is well-established. As a result, doctors are familiar with the drug, even when it is tested for a new purpose in sickle cell anemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell anemia?

Imatinib Mesylate is unique because it offers a novel approach to treating sickle cell anemia by targeting specific cellular pathways. Unlike traditional treatments that primarily focus on managing symptoms and preventing complications, such as hydroxyurea or blood transfusions, Imatinib works at the cellular level to potentially address the root cause of the disease. Researchers are excited about this treatment because it targets the signaling pathways involved in red blood cell deformation, which could improve blood flow and reduce painful episodes. This new mechanism of action has the potential to offer more effective disease management and improve the quality of life for patients with sickle cell anemia.

What evidence suggests that imatinib might be an effective treatment for sickle cell anemia?

Research has shown that imatinib mesylate, which participants in this trial will receive, might help reduce pain in people with sickle cell anemia. One study found that patients taking imatinib had fewer painful episodes. In animal tests, imatinib reduced damage to blood cells and inflammation. Early results from human patients suggested fewer painful crises and less need for pain medication. These findings indicate that imatinib could be a promising treatment for managing symptoms of sickle cell disease. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imatinib mesylate orally to evaluate its biochemical effects on sickle RBCs

6 months

Monthly visits for monitoring and evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Imatinib Mesylate

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.

How Is the Trial Designed?

Group I: Imatinib Intervention Experimental Treatment 1 Intervention

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

Approved in United States as Gleevec for:

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

Approved in European Union as Glivec for:

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

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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 (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 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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2531137923001475

Impact of Imatinib on reducing the painful crisis in patients ... Our data demonstrated that consumption of imatinib significantly reduced chronic pain without any significant changes in hematological variables. In addition, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9977487/

In Humanized Sickle Cell Mice, Imatinib Protects Against ... These data indicate that imatinib reduces H/R-induced hemolysis and positively modulates systemic inflammatory response, preventing neutrophils ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03997903

NCT03997903 | Imatinib for Pain in Sickle Cell Anemia The investigators expect band 3 tyrosine phosphorylation to decrease dramatically in patients treated with imatinib.

4. hematologyadvisor.com hematologyadvisor.com/news/sickle-cell-disease-treatment-using-tyrosine-kinase-inhibition/

Imatinib as Potential Tyrosine Kinase Inhibitor to Treat ... Syk tyrosine kinase inhibitors (TKIs), such as imatinib, may be effective in treating sickle cell disease (SCD), according to research ...

5. researchgate.net researchgate.net/publication/336398436_Effectiveness_of_Imatinib_Therapy_for_a_Patient_with_Sickle_Cell_Anemia_and_Chronic_Myelocytic_Leukemia

Effectiveness of Imatinib Therapy for a Patient with Sickle ... In the 17 months since initiation of imatinib, the patient has had a significant reduction in the frequency of painful episodes. No ...

6. d197for5662m48.cloudfront.net d197for5662m48.cloudfront.net/documents/publicationstatus/274695/preprint_pdf/668e58de094ececb94f9884eba3dacba.pdf

Drug Repurposing in Sickle Cell Disease: Evaluating Imatinib ... The drug repurposing pathway of imatinib in SCD is still in its early stages and may not necessarily lead to a definitive outcome. • Imatinib ...

7. withpower.com withpower.com/trial/early-phase-1-anemia-sickle-cell-1-2020-a6071

Imatinib for Sickle Cell Anemia (IMPACT Trial) Common mild side effects include nausea, myalgia, edema, muscle cramps, and gastrointestinal symptoms. Severe adverse effects are rare, and most side effects ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11451392/

Impact of Imatinib on reducing the painful crisis in patients with ... Our data demonstrated that consumption of imatinib significantly reduced chronic pain without any significant changes in hematological variables.

9. ashpublications.org ashpublications.org/bloodadvances/article/3/23/3982/429244/End-points-for-sickle-cell-disease-clinical-trials

End points for sickle cell disease clinical trials End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain. Blood Adv (2019) 3 (23): 3982–4001.