Ivosidenib for Blood Disorders
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
Must not be taking: CYP3A4 inducers
Disqualifiers: Active malignancy, Solid tumor therapy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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.
12345What 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.
678910Is 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.
2351112Eligibility 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.
+5 more
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.
+8 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: IvosidenibExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwell Health Cancer Institute (R.J. Zuckerberg Cancer Center)Lake Success, NY
Mayo ClinicRochester, MN
OHSU Knight Cancer InstitutePortland, OR
Washington University School of MedicineSaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
Servier Hellas Pharmaceuticals Ltd.Industry Sponsor
Gateway for Cancer ResearchCollaborator
References
Recombinant human thrombopoietin promotes platelet recovery in DCAG-treated patients with intermediate-high-risk MDS/hypoproliferative AML. [2023]This study aimed to explore the effects of recombinant human thrombopoietin (rhTPO) on platelet recovery in decitabine, cytarabine, aclarubicin, and G-CSF (DCAG)-treated patients with intermediate-high-risk myelodysplastic syndrome/hypo proliferative acute myeloid leukemia.
Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. [2016]To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS).
Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. [2022]Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies.
Romiplostim or standard of care in patients with immune thrombocytopenia. [2016]Romiplostim, a thrombopoietin mimetic, increases platelet counts in patients with immune thrombocytopenia, with few adverse effects.
Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. [2020]To determine the efficacy of the thrombopoietin receptor agonist romiplostim for the prevention of temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma.
Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in polycythaemia vera. [2019]We report on long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia vera (PV). In all patients haematocrit was first brought into the normal range by venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU. Complete response (CR) was defined as persistence of normal haematocrit without venesection and partial response (PR) as >50% reduction of phlebotomy requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median duration of treatment for all responsive patients was 40 months; 12 patients are still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50, 51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN-alpha also normalized leucocyte counts, platelet counts and spleen enlargement; rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment suspension in all cases. Progression to leukaemia was observed in none of the 10 patients treated only with rIFN-alpha and in one of the 12 who received alkylating agents before enrolment in this study. According to these data, rIFN-alpha seems to be an effective and safe treatment option for PV.
Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. [2022]Interferon-alpha (IFN-alpha) is a nonleukemogenic treatment of polycythemia vera (PV) able to induce cytogenetic remissions. Its use is limited by toxicity, leading to treatment discontinuation in approximately 20% of patients. We completed a phase 2 multicenter study of pegylated IFN-alpha-2a in 40 PV patients. Objectives included evaluation of efficacy, safety, and monitoring of residual disease using JAK2V617F quantification (%V617F). Median follow-up was 31.4 months. At 12 months, all 37 evaluable patients had hematologic response, including 94.6% complete responses (CRs). Only 3 patients (8%) had stopped treatment. After the first year, 35 patients remained in hematologic CR, including 5 who had stopped pegylated IFN-alpha-2a. Sequential samples for %V617F monitoring, available in 29 patients, showed %V617F decrease in 26 (89.6%). Median %V617F decreased from 45% before pegylated IFN-alpha-2a to 22.5%, 17.5%, 5%, and 3% after 12, 18, 24, and 36 months, respectively. Molecular CR (JAK2V617F undetectable) was achieved in 7 patients, lasting from 6(+) to 18(+) months, and persisted after pegylated IFN-alpha-2a discontinuation in 5. No vascular event was recorded. These results show that pegylated IFN-alpha-2a yields high rates of hematologic and molecular response in PV with limited toxicity, and could even eliminate the JAK2 mutated clone in selected cases. Available at www.clinicaltrials.gov as #NCT00241241.
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts
Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies. [2020]The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115-316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.
Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. [2022]Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PV who were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 months were 69.2% (43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P = .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was -6% (range, -84% to 47%) in patients achieving a CR vs +4% (range, -18% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU. This trial was registered at www.clinicaltrials.gov as #NCT01259856.
Moving towards a new era in the management of chronic immune thrombocytopenia. [2016]Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease in which a low concentration of plasma thrombopoietin (TPO) contributes to the thrombocytopenia. Functional thrombopoietin deficiency in response to thrombocytopenia is central to the pathophysiology of chronic ITP. Decreased platelet production in ITP patients has been described only in recent years, however. Following the development of TPO-mimetics, it has become clear that the augmentation of thrombopoiesis is a key therapeutic target. TPO mimetics are novel effective treatments providing durable platelet responses in ITP. Two agents have reached clinical practice, the 'peptibody' romiplostim (Nplate(R)) approved for treatment of thrombocytopenia in patients with chronic ITP in Europe, Canada, Australia and the USA and the non-peptide TPO mimetic, eltrombopag (Promacta(R)), approved in the USA. This review summarises the background to the development of these agents and presents an update on data from randomised phase III trials and open-label studies. These novel drugs provide a noteworthy treatment option for patients with chronic ITP, in whom thrombocytopenia and bleeding risk have not been controlled by standard treatments. The first candidates for treatment in clinical practice are undoubtedly refractory patients with lack of response to other therapies or at continued risk for bleeding despite treatment. Appropriate inclusion of TPO mimetics into the treatment paradigm will most likely have a positive impact on the long-term outcome of ITP and allow carefully monitored patients to remain well controlled, with good tolerability for prolonged periods.
Romiplostim dose-response in patients with myelodysplastic syndromes. [2021]To characterize the romiplostim dose-response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim.