Thrombocytopenic Purpura > Eltrombopag

Ianalumab + Eltrombopag for Low Platelet Count

(VAYHIT2 Trial)

Recruiting in Palo Alto (17 mi)

+130 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novartis Pharmaceuticals

Must be taking: Eltrombopag

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: HIV, Hepatitis, Coagulation disorders, others

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antiplatelet or anticoagulant medications, you may need to stop them unless it's a low dose of acetylsalicylic acid (up to 150 mg daily).

How is the drug combination of Ianalumab and Eltrombopag unique for treating low platelet count?

The combination of Ianalumab and Eltrombopag is unique because it combines a monoclonal antibody (Ianalumab) with a thrombopoietin receptor agonist (Eltrombopag), potentially offering a novel approach to stimulate platelet production and modulate the immune system, which may differ from standard treatments that typically focus on one mechanism.

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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.

Inclusion Criteria

I am 18 years or older.

A signed informed consent must be obtained prior to participation in the study

My platelet count is below 30G/L and I can take eltrombopag.

Exclusion Criteria

I have ITP and have tried treatments beyond steroids, including having my spleen removed.

I have a history of severe bleeding.

I have liver problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Treatment

Participants receive ianalumab or placebo in addition to eltrombopag

24 weeks

Regular visits for monitoring and dose adjustments

Eltrombopag Tapering

Participants undergo tapering of eltrombopag

Up to 24 weeks

Regular visits for monitoring tapering process

Follow-up

Participants are monitored for efficacy and safety after treatment

Up to 39 months

Periodic visits for long-term monitoring

Participant Groups

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.

Group I: Treatment arm 2 Experimental Treatment 2 Interventions

Participants will receive eltrombopag and ianalumab higher dose

Group II: Treatment arm 1 Experimental Treatment 2 Interventions

Participants will receive eltrombopag and ianalumab lower dose

Group III: Treatment arm 3 Placebo Group 2 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 Nearby Select from list below to view details:

UMASS Memorial Medical Center Worcester, MA

Uni of Chi Medi Ctr Hema and Onco Main Centre Chicago, IL

Texas Oncology Drug Ship 5 Dallas, TX

St Vincent Frontier Cancer Center . Billings, MT

More Trial Locations

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals Lead Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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.

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

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.

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

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.

4. New Zealand pubmed.ncbi.nlm.nih.gov

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.

5. Germany pubmed.ncbi.nlm.nih.gov

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.