Ianalumab + Eltrombopag for Low Platelet Count (VAYHIT2 Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Novartis Pharmaceuticals
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in adults with primary ITP who failed previous first-line treatment with steroids.
What safety data exists for the treatment of Ianalumab + Eltrombopag for low platelet count?The provided research does not contain any safety data for the treatment of Ianalumab (also known as VAY736, NOV-5, NVP-VAY736) combined with Eltrombopag (also known as Promacta, Revolade) for low platelet count. The articles focus on other treatments and conditions, such as tisotumab vedotin for cervical cancer, lenvatinib with pembrolizumab for endometrial carcinoma, and enfortumab vedotin for urothelial carcinoma.5891013
Is the drug Eltrombopag, Ianalumab a promising treatment for low platelet count?The information provided does not include any details about Eltrombopag or Ianalumab, so we cannot determine if it is a promising treatment for low platelet count based on the given research articles.2381113
What data supports the idea that Ianalumab + Eltrombopag for Low Platelet Count is an effective treatment?The available research does not provide any data on the effectiveness of Ianalumab + Eltrombopag for Low Platelet Count. The studies focus on other treatments and conditions, such as cancer-related issues and anticoagulation therapies, but do not mention Ianalumab + Eltrombopag or its effectiveness for low platelet count.146712
Do I have to stop taking my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on antiplatelet or anticoagulant medication, except for low-dose acetylsalicylic acid (≤150 mg daily).
Eligibility Criteria
Adults over 18 with primary immune thrombocytopenia (ITP) who didn't respond well to steroids can join. They must have a low platelet count and be eligible for eltrombopag treatment. People with coagulation disorders, other cytopenias, significant blood diseases, life-threatening bleeding history, or positive HIV/HCV cannot participate.Treatment Details
The trial is testing how effective two doses of ianalumab are when added to eltrombopag in prolonging the time before ITP treatment fails after steroid therapy doesn’t work. Participants will either receive ianalumab or a placebo alongside eltrombopag.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Treatment arm 2Experimental Treatment2 Interventions
Participants will receive eltrombopag and ianalumab higher dose
Group II: Treatment arm 1Experimental Treatment2 Interventions
Participants will receive eltrombopag and ianalumab lower dose
Group III: Treatment arm 3Placebo Group2 Interventions
Participants will receive eltrombopag and placebo
Eltrombopag is already approved in United States, European Union, Canada, Japan, China for the following indications:
🇺🇸 Approved in United States as Promacta for:
- Severe aplastic anemia
- Chronic immune thrombocytopenia
- Thrombocytopenia in patients with chronic hepatitis C
🇪🇺 Approved in European Union as Revolade for:
- Severe aplastic anemia
- Chronic immune thrombocytopenia
🇨🇦 Approved in Canada as Promacta for:
- Severe aplastic anemia
- Chronic immune thrombocytopenia
🇯🇵 Approved in Japan as Revolade for:
- Severe aplastic anemia
- Chronic immune thrombocytopenia
🇨🇳 Approved in China as Promacta for:
- Severe aplastic anemia
- Chronic immune thrombocytopenia
Find a clinic near you
Research locations nearbySelect from list below to view details:
UMASS Memorial Medical CenterWorcester, MA
Uni of Chi Medi Ctr Hema and Onco Main CentreChicago, IL
Texas Oncology Drug Ship 5Dallas, TX
St Vincent Frontier Cancer Center .Billings, MT
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Who is running the clinical trial?
Novartis PharmaceuticalsLead Sponsor
References
Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study. [2018]Background There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin. Methods Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality. Results Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively. Conclusion The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. [2022]Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT.
Antisense targeting of CD47 enhances human cytotoxic T-cell activity and increases survival of mice bearing B16 melanoma when combined with anti-CTLA4 and tumor irradiation. [2021]Antibodies targeting the T-cell immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA4) enhance the effectiveness of radiotherapy for melanoma patients, but many remain resistant. To further improve response rates, we explored combining anti-CTLA4 blockade with antisense suppression of CD47, an inhibitory receptor on T cells that limit T-cell receptor signaling and killing of irradiated target cells. Human melanoma data from The Cancer Genome Atlas revealed positive correlations between CD47 mRNA expression and expression of T-cell regulators including CTLA4 and its counter receptors CD80 and CD86. Antisense suppression of CD47 on human T cells in vitro using a translational blocking morpholino (CD47 m) alone or combined with anti-CTLA4 enhanced antigen-dependent killing of irradiated melanoma cells. Correspondingly, the treatment of locally irradiated B16F10 melanomas in C57BL/6 mice using combined blockade of CD47 and CTLA4 significantly increased the survival of mice relative to either treatment alone. CD47 m alone or in combination with anti-CTLA4 increased CD3+ T-cell infiltration in irradiated tumors. Anti-CTLA4 also increased CD3+ and CD8+ T-cell infiltration as well as markers of NK cells in non-irradiated tumors. Anti-CTLA4 combined with CD47 m resulted in the greatest increase in intratumoral granzyme B, interferon-γ, and NK-cell marker mRNA expression. These data suggest that combining CTLA4 and CD47 blockade could provide a survival benefit by enhancing adaptive T- and NK-cell immunity in irradiated tumors.
Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis. [2021]International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE.
FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]On December 18, 2019, the FDA granted accelerated approval to enfortumab vedotin-ejfv (PADCEV; Astellas and Seattle Genetics) for treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a programmed cell death protein 1 or programmed death ligand 1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Substantial evidence of effectiveness for this application is obtained from Cohort 1 of the single-arm, multicenter Study EV-201. Patients received enfortumab vedotin (EV) 1.25 mg/kg (up to a maximum dose of 125 mg) intravenously on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Confirmed objective response rate in the 125-patient efficacy population determined by blinded independent central review was 44% [95% confidence interval (CI), 35.1-53.2], with complete responses in 12%. Median response duration was 7.6 months (95% CI, 6.3-not estimable). Grade 3-4 adverse reactions occurred in 73% of patients. Hyperglycemia, peripheral neuropathy, ocular disorders, skin reactions, infusion site extravasations, and embryo-fetal toxicity are labeled as warnings and precautions for EV. The article summarizes the data and the FDA thought process supporting accelerated approval of EV. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Effectiveness and Safety of Apixaban, Low-Molecular-Weight Heparin, and Warfarin among Venous Thromboembolism Patients with Active Cancer: A U.S. Claims Data Analysis. [2021]This study primarily evaluates the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular-weight heparin (LMWH), or warfarin, with claims data.
Anticoagulation with Factor Xa Inhibitors Is Associated with Improved Overall Response and Progression-Free Survival in Patients with Metastatic Malignant Melanoma Receiving Immune Checkpoint Inhibitors-A Retrospective, Real-World Cohort Study. [2021]Immune checkpoint inhibitors (ICI) significantly improved the prognosis of advanced melanoma patients. However, many patients do not derive long-term benefit from ICI therapy due to primary and acquired resistance. In this regard, it has been shown that coagulation factors contribute to cancer immune evasion and might therefore promote resistance to ICI. In particular, recent observations in murine systems demonstrated that myeloid-derived factor Xa (FXa) impedes anti-tumor immunity in the tumor microenvironment and that the oral FXa inhibitor (FXa-i) rivaroxaban synergizes with ICI. The synergistic effect of FXa inhibitors with clinical ICI therapy is unknown. We performed a retrospective study of 280 metastatic melanoma patients who were treated with ICI and stratified them for concomitant anticoagulation (AC) by medical chart review. Data on baseline patient characteristics, specific AC treatment, ICI therapy, other tumor-targeting therapies, and clinical outcomes were analyzed. Of 280 patients who received ICI, 76 received concomitant AC during initial ICI therapy. Patients on AC were treated either with heparins (n = 29), vitamin K antagonists (VKA) (n = 20), or FXa-i (n = 27). Patients requiring AC during ICI therapy showed no significantly reduced objective response rate (ORR) (p = 0.27), or progression-free (PFS; median PFS 4 vs. 4 months; p = 0.71) or overall survival (OS; median OS: 39 vs. 51 months; p = 0.31). Furthermore, patients who underwent AC did not show significantly more bleeding complications (p = 0.605) than those who were not anticoagulated. Remarkably, stratification of patients by the class of AC revealed that patients receiving FXa-i were more likely to obtain CR (26.9 vs. 12.6%, p = 0.037), and showed better ORR (69.2 vs. 36.4%, p = 0.005), PFS (median PFS: 12 months vs. 3 months; p = 0.006), and OS (median OS not reached vs. 42 months; p = 0.09) compared to patients not receiving FXa-i. Patient demographics and tumor characteristics in this patient subcohort did not significantly differ from patients not on FXa-i. In summary, our study provides first clinical evidence that the clinical application of FXa-i may enhance the efficacy of ICI therapy via the restoration of anti-tumor immunity, while patients who received FXa-i were not more likely to encounter bleeding complications.
A Review of Tisotumab Vedotin-tftv in Recurrent or Metastatic Cervical Cancer. [2023]To evaluate the safety and efficacy of tisotumab vedotin-tftv (TV), a first-in-class vectorized anti-tissue factor (TF) antibody-drug conjugate (ADC), for the treatment of recurrent or metastatic cervical cancer.
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.
Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. [2023]The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC).
Tremelimumab: First Approval. [2023]Tremelimumab (tremelimumab-actl; IMJUDO®), a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody, is being developed by AstraZeneca, under license from Pfizer, for the treatment of a range of malignant tumours. Tremelimumab was approved in the USA in October 2022 in combination with durvalumab for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). In addition, tremelimumab in combination with durvalumab and platinum-based chemotherapy was approved in the USA in November 2022 for the treatment of adult patients with metastatic non-small cell lung cancer (mNSCLC) with no sensitizing epidermal growth factor receptor mutation or anaplastic lymphoma kinase genomic tumour aberrations. In December 2022, tremelimumab in combination with durvalumab received a Positive Opinion from the EU Committee for Medicinal Products for Human Use for the first line treatment of adults with advanced or unresectable HCC. Tremelimumab in combination with durvalumab is under regulatory review for these indications in Japan and in other countries worldwide. This article summarizes the milestones in the development of tremelimumab leading to this first approval.
Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding. [2023]This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.
Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data. [2023]Cervical cancer is the fourth most common type of cancer in women worldwide. It is associated with a high death rate, despite the fact that it is a nearly 100% preventable disease because of very effective primary and secondary preventive strategies. Advanced and recurrent disease is uncurable with a high relapse risk and the second-line therapies are limited with modest response rates and short durability. Investigating alternative mechanisms of action is crucial because of the high request for effective new therapies. Tisotumab vedotin (TV) is the first antibody-drug conjugated to target a cell surface-expressed tissue factor, and preliminary data in patients with metastatic and recurrent cervical cancer have been promising. In addition, the trials showed a favorable tolerability profile, with limited incidence of grade 3 or worse adverse events. According to the data of ENGOT-cx6/GOG-3023/innovaTV 204, the US Food and Drug Administration granted expedited approval of TV on September 20, 2021, for women with recurrent or metastatic cervical cancer. Actually, two other trials testing TV alone or in combination with other agents are ongoing. ENGOT-cx8/GOG-3024/innovaTV 205 is a Phase Ib/II trial of TV in combination with platinum or bevacizumab or pembrolizumab, in patients with recurrent or metastatic cervical cancer who have not received prior systemic therapy or who have progressed after no more than two prior systemic therapies. ENGOT-cx12/GOG-3057/InnovaTV 301 is a Phase 3 trial of TV vs investigator's choice chemotherapy in patients with advanced or recurrent cervical cancer who had received no more than 2 prior chemotherapy lines. The outcomes of these two trials will potentially confirm and reinforce the use of TV as a new standard of care in advanced or recurrent cervical cancer.