Ivosidenib for Blood Disorders

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ivosidenib (Tibsovo) to determine its effectiveness for people with clonal cytopenia of undetermined significance (CCUS). CCUS leads to low blood cell counts, and the study aims to assess whether ivosidenib can improve these counts and ensure its safety. Ideal participants have experienced unexplained low blood cell counts for over six months and possess a specific IDH1 gene mutation. The trial is conveniently conducted remotely. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

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

Research has shown that ivosidenib, the treatment under study, has been tested in patients with other conditions, such as cholangiocarcinoma (a type of bile duct cancer). In these patients, the most common side effects included tiredness, nausea, stomach pain, and diarrhea, occurring in at least 15% of patients. Most side effects were mild to moderate, indicating they were not very serious.

In another group of patients with a different blood disorder, serious side effects were less common, with only 5% of patients experiencing them. This suggests that while some side effects can occur, they are usually not severe for most people.

Ivosidenib is also approved by the FDA for other conditions, indicating it has been studied for safety. However, discussing potential risks and benefits with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ivosidenib is unique because it targets a specific genetic mutation found in certain blood disorders, called IDH1. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Ivosidenib works by inhibiting the mutant IDH1 enzyme, potentially leading to fewer side effects. Researchers are excited about this treatment because it offers a more precise approach, which could improve outcomes and quality of life for patients with these specific genetic profiles.

What evidence suggests that ivosidenib might be an effective treatment for blood disorders?

Research shows that ivosidenib, which participants in this trial will receive, may help treat certain blood disorders. In studies with patients who have a specific type of myelodysplastic syndrome (a condition affecting blood cell production) with IDH1 mutations, ivosidenib led to complete remission in 38.9% of cases and an overall improvement in 83.3% of patients. Many patients experienced significant improvements in their condition. Additionally, those treated with ivosidenib recovered blood health more quickly and for longer periods, including better blood counts and reduced need for blood transfusions. These results suggest that ivosidenib might also improve blood count issues in patients with clonal cytopenia of undetermined significance (CCUS) who have similar genetic mutations. ^{6 7 8 9 10}

Who Is on the Research Team?

Kelly Bolton, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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 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 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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38640348/

Final phase 1 substudy results of ivosidenib for patients ... We report final data from a phase 1 single-arm substudy of once-daily ivosidenib in patients with R/R mIDH1 myelodysplastic syndrome (MDS) after ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/15/4209/515789/Final-phase-1-substudy-results-of-ivosidenib-for

Final phase 1 substudy results of ivosidenib for patients with ... Ivosidenib resulted in a CR rate of 38.9% and an OR rate of 83.3% in mIDH1 R/R MDS; median duration of response was not reached.

3. servier.us servier.us/blog/servier-presents-updated-results-for-tibsovo-ivosidenib-tablets-in-idh1-mutated-relapsed-refractory-myelodysplastic-syndromes-at-the-2023-european-hematology-association-eha-congress/

Servier Presents Updated Results for TIBSOVO ... In the efficacy analysis set (n=18), a complete remission (CR) rate of 38.9% and overall response rate (ORR) of 83.3% were documented in ...

4. tibsovopro.com tibsovopro.com/mds/efficacy

TIBSOVO® (ivosidenib tablets) Efficacy R/R mIDH1 MDS 39% · Durability of remissions with TIBSOVO · Patients treated with TIBSOVO achieved hematologic improvements, including rapid neutrophil recovery ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40706052/

Long-term results from the AGILE study of azacitidine plus ... Hematologic recovery was faster, more durable, and conversion to transfusion independence (53.8% vs 17.1%; P = .0004) was more common with ivosidenib than with ...

6. tibsovopro.com tibsovopro.com/cca/safety

Safety Profile | CCA - TIBSOVO® (ivosidenib tablets) The most common adverse reactions (≥15%) in patients with advanced mIDH1 cholangiocarcinoma (CCA) were fatigue, nausea, abdominal pain, diarrhea, cough, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/211192_s008lbl.pdf

TIBSOVO (ivosidenib tablets - accessdata.fda.gov The most common adverse reactions (≥15%) in patients with cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, ...

8. tibsovopro.com tibsovopro.com/mds/safety

TIBSOVO® (ivosidenib tablets) Safety in R/R mIDH1 MDS The majority of adverse reactions with TIBSOVO were Grades 1 or 2 · Serious adverse reactions in ≥5% of patients included differentiation syndrome (11%), fatigue ...

9. tibsovo.com tibsovo.com/

TIBSOVO® (ivosidenib tablets) It is not known if TIBSOVO is safe and effective in children. ... Your healthcare provider will do blood tests before you start and during treatment with TIBSOVO.

10. tibsovo.com tibsovo.com/pdf/prescribinginformation.pdf

Prescribing Information In this safety population, the most common adverse reactions including laboratory abnormalities (≥ 25% in either trial) were leukocytes decreased, diarrhea, ...