Ivosidenib for Blood Disorders

Recruiting at 5 trial locations

Overseen By Kelly Bolton, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: CYP3A4 inducers

Disqualifiers: Active malignancy, Solid tumor therapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called ivosidenib in patients with a specific blood condition and a genetic mutation. The goal is to see if the medication can safely improve their blood counts. The study is also designed to be conducted remotely. Ivosidenib has shown significant improvements in patients with certain types of cancers.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take medications that are CYP3A4 strong inducers and sensitive substrates.

What data supports the idea that Ivosidenib for Blood Disorders is an effective drug?

The available research does not provide specific data on the effectiveness of Ivosidenib for Blood Disorders. Instead, it focuses on other treatments like romiplostim and rilzabrutinib, which are used to increase platelet counts in various blood disorders. Without direct data on Ivosidenib, we cannot compare its effectiveness to these alternatives. ^{1 2 3 4 5}

What safety data is available for Ivosidenib (Tibsovo) in treating blood disorders?

The provided research does not contain specific safety data for Ivosidenib (Tibsovo) in treating blood disorders. The studies focus on other treatments like interferon-alpha and ruxolitinib for conditions such as polycythemia vera and myelofibrosis. For Ivosidenib, safety data would need to be sourced from clinical trials or studies specifically evaluating this drug. ^{6 7 8 9 10}

Is the drug Ivosidenib (Tibsovo) a promising treatment for blood disorders?

The provided research articles do not mention Ivosidenib (Tibsovo) as a treatment for blood disorders. They focus on other treatments like romiplostim and rilzabrutinib for conditions like immune thrombocytopenia and myelodysplastic syndromes. Therefore, based on this information, we cannot say if Ivosidenib is a promising treatment for blood disorders. ^{2 3 5 11 12}

Research Team

Kelly Bolton, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with clonal cytopenia of undetermined significance (CCUS) and specific IDH1 gene mutations who have had unexplained low blood counts for at least six months. Participants must be in stable health, not pregnant or breastfeeding, without active cancer or heart issues, and able to consent.

Inclusion Criteria

My cancer has a specific IDH1 gene mutation.

I have had low blood counts for over 6 months without a known cause.

My cancer has a specific IDH1 gene mutation.

Exclusion Criteria

My most recent scan shows cancer larger than 1 cm.

I do not have any uncontrolled illnesses like infections or heart problems.

I have a history of PML.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivosidenib at a dose of 500 mg daily for up to 5 years, with each cycle lasting 28 days

60 months

Decentralized, remote structure

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Treatment Details

Interventions

• Ivosidenib

Trial Overview The trial is testing Ivosidenib's safety and effectiveness in improving blood count abnormalities in patients with CCUS carrying IDH1 mutations. It's an open-label study where all participants receive the drug, conducted remotely across multiple centers.

Participant Groups

Group I: Ivosidenib Experimental Treatment 1 Intervention

-Ivosidenib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg daily for up to 5 years. Each cycle is 28 days.

Ivosidenib is already approved in United States, European Union for the following indications:

Approved in United States as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Approved in European Union as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Servier Hellas Pharmaceuticals Ltd.

Industry Sponsor

Trials

2

Recruited

2,300+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Findings from Research

Recombinant human thrombopoietin (rhTPO) significantly accelerates platelet recovery in patients treated with DCAG for myelodysplastic syndrome or acute myeloid leukemia, with recovery times to ≥20, ≥30, and ≥50 × 10^9/L being shorter compared to the control group.

Patients receiving rhTPO required fewer platelet transfusions and experienced lower bleeding scores, while also showing improved overall survival (OS) and progression-free survival (PFS) compared to those not receiving rhTPO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human thrombopoietin promotes platelet recovery in DCAG-treated patients with intermediate-high-risk MDS/hypoproliferative AML. Chen, X., Wang, Y., Zang, Y., et al.[2023]

Romiplostim, a treatment aimed at increasing platelet production, showed a significant increase in platelet counts among 44 patients with lower-risk myelodysplastic syndromes (MDS), with 46% achieving a durable platelet response over 8 weeks.

The treatment was generally well-tolerated, with a low incidence of bleeding events in patients who responded positively, although 11% of patients experienced serious adverse events, particularly at the highest dose of 1,500 microg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. Kantarjian, H., Fenaux, P., Sekeres, MA., et al.[2016]

In a phase 1-2 clinical trial involving 60 patients with immune thrombocytopenia, rilzabrutinib demonstrated a platelet response in 40% of participants, indicating its efficacy in increasing platelet counts through dual mechanisms of action.

The treatment was well-tolerated, with only low-level, transient side effects and no serious bleeding or thrombotic events, suggesting a favorable safety profile for further testing at the identified effective dose of 400 mg twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. Kuter, DJ., Efraim, M., Mayer, J., et al.[2022]

In a 52-week study involving 234 adults with immune thrombocytopenia, romiplostim significantly increased the rate of platelet response compared to standard care, with a response rate 2.3 times higher (P<0.001).

Patients receiving romiplostim experienced fewer treatment failures and required splenectomy less often (11% vs. 30% for standard care, P<0.001), along with lower rates of bleeding events and improved quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim or standard of care in patients with immune thrombocytopenia. Kuter, DJ., Rummel, M., Boccia, R., et al.[2016]

In a phase II trial involving 20 patients with glioblastoma, romiplostim significantly improved the ability of patients to complete 6 cycles of temozolomide chemotherapy, achieving a success rate of 60%.

Romiplostim was effective in preventing temozolomide-induced thrombocytopenia, allowing more patients to continue their chemotherapy treatment, which is crucial for managing glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. Le Rhun, E., Devos, P., Houillier, C., et al.[2020]

In a study of 38 patients with polycythemia vera, recombinant interferon-alpha 2a (rIFN-alpha) demonstrated long-term efficacy, with 28.9% achieving complete response and 21.0% achieving partial response after a median treatment duration of 40 months.

rIFN-alpha was effective in normalizing blood counts and alleviating symptoms like pruritus, with manageable toxicity; only 23.6% experienced early flu-like symptoms and 13.1% had late severe weakness, indicating it is a safe treatment option for polycythemia vera.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in polycythaemia vera. Foa, P., Massaro, P., Caldiera, S., et al.[2019]

In a phase 2 study involving 40 patients with polycythemia vera, pegylated interferon-alpha-2a demonstrated high efficacy, with 94.6% of evaluable patients achieving complete hematologic responses after 12 months and 89.6% showing a decrease in the JAK2V617F mutation.

The treatment was well-tolerated, with only 8% of patients discontinuing due to toxicity, and no vascular events reported, indicating that pegylated interferon-alpha-2a is a safe and effective option for managing polycythemia vera.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Kiladjian, JJ., Cassinat, B., Chevret, S., et al.[2022]

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

A review of 35 new drugs for hematological malignancies revealed that 80% had postmarketing safety-related label modifications, indicating that many drugs may have unrecognized side effects after approval.

Most of these drugs were approved based on limited evidence, with 77% not supported by randomized controlled trials, highlighting the need for caution among hematologists when prescribing these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies. Gafter-Gvili, A., Tibau, A., Raanani, P., et al.[2020]

In a phase 2 trial involving 115 patients with essential thrombocythemia (ET) and polycythemia vera (PV) who were previously treated with hydroxyurea, pegylated interferon-α2a (PEG) therapy achieved overall response rates of 69.2% in ET and 60% in PV after 12 months, indicating its efficacy in these high-risk patients.

The therapy was generally well-tolerated, with only 13.9% of patients discontinuing due to adverse events, suggesting that PEG is a safe and effective option for patients who are refractory or intolerant to hydroxyurea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Yacoub, A., Mascarenhas, J., Kosiorek, H., et al.[2022]

TPO mimetics, such as romiplostim and eltrombopag, are effective new treatments for immune thrombocytopenia (ITP), significantly improving platelet production and providing durable responses in patients who do not respond to standard therapies.

These treatments are particularly beneficial for patients with chronic ITP who are at high risk for bleeding, suggesting that incorporating TPO mimetics into treatment plans can enhance long-term management and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving towards a new era in the management of chronic immune thrombocytopenia. Wadenvik, H., Olsson, B.[2016]

In a study of 44 subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS), subcutaneous romiplostim demonstrated a linear dose-response relationship, effectively increasing platelet counts in 78% of responders.

The pharmacodynamic model revealed that romiplostim significantly stimulates the production of progenitor cells, with an average increase of 269% in production rate per 100 μg per week, indicating its efficacy in managing low platelet counts in MDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim dose-response in patients with myelodysplastic syndromes. Perez Ruixo, JJ., Doshi, S., Wang, YM., et al.[2021]

References

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

Recombinant human thrombopoietin promotes platelet recovery in DCAG-treated patients with intermediate-high-risk MDS/hypoproliferative AML. [2023]

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

Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. [2016]

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

Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. [2022]

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

Romiplostim or standard of care in patients with immune thrombocytopenia. [2016]

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

Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in polycythaemia vera. [2019]

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

Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. [2022]

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

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies. [2020]

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

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Moving towards a new era in the management of chronic immune thrombocytopenia. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Romiplostim dose-response in patients with myelodysplastic syndromes. [2021]