Romiplostim for Chemotherapy-Induced Low Platelet Count

Recruiting in Palo Alto (17 mi)

+101 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Amgen

Must be taking: Carboplatin-based chemotherapy

Must not be taking: TPO receptor agonists

Disqualifiers: Leukemia, Myeloma, Heart failure, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests romiplostim, a drug that boosts platelet production, in adults with certain cancers undergoing chemotherapy. It aims to help these patients maintain their chemotherapy schedule by increasing their platelet counts. Romiplostim has shown effectiveness in increasing platelet counts in patients with low platelet levels due to chemotherapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that certain investigational drugs or treatments cannot be taken concurrently, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Romiplostim for treating low platelet counts caused by chemotherapy?

Research shows that Romiplostim, originally approved for immune thrombocytopenia, has been used off-label for chemotherapy-induced low platelet counts. In a study, 51% of patients achieved a significant increase in platelet count within a week, suggesting its potential effectiveness for this condition. ^{1 2 3 4 5}

How does the drug romiplostim differ from other treatments for low platelet count due to chemotherapy?

Romiplostim is unique because it is a thrombopoietin receptor agonist, which means it stimulates the body's production of platelets by mimicking a natural protein that encourages platelet growth. Unlike other treatments, it is administered as a weekly injection and is specifically designed to increase platelet counts in patients who have not responded well to other therapies. ^{2 4 5 6 7}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Adults over 18 with advanced or recurrent NSCLC, breast, or ovarian cancer eligible for chemotherapy can join. They must have low platelet counts due to chemo and be able to undergo at least 3 more cycles. Exclusions include HIV, recent heart issues, other cancers within 5 years (with exceptions), active infections, certain blood disorders, and unwillingness to use contraception.

Inclusion Criteria

Your platelet count must be less than or equal to 85,000 on the first day of the study.

I finished my last chemotherapy cycle at least 21 or 28 days ago, depending on the cycle length.

I am 18 years or older.

Exclusion Criteria

Currently receiving (or plan to receive) treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

I am undergoing a treatment plan that includes chemotherapy along with radiation therapy or surgery.

I have multiple myeloma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive romiplostim or placebo during chemotherapy cycles to assess efficacy in treating chemotherapy-induced thrombocytopenia

10-24 weeks

Administered in the clinic by a qualified healthcare provider

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 days

Long-term Follow-up

Participants are monitored for secondary malignancies, adverse events, and other long-term outcomes

Up to 36 months

Treatment Details

Interventions

• Romiplostim (Thrombopoietin Receptor Agonist)

Trial Overview The trial is testing Romiplostim's effectiveness in treating low platelet counts caused by chemotherapy in patients with NSCLC, ovarian cancer, or breast cancer. The goal is to see if it helps them receive full-dose chemo on schedule without delays.

Participant Groups

Group I: Romiplostim Experimental Treatment 1 Intervention

The study in a 2:1 randomization ratio(108 subjects to romiplostim). Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.

Group II: Placebo Placebo Group 1 Intervention

The study in a 2:1 randomization ratio (54 subjects to placebo) Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

In a study of 84 adult patients at NYU Langone Health, romiplostim was used off-label for conditions like chemotherapy-induced thrombocytopenia and post-hematopoietic stem cell transplantation, with a median initial dose of 3.8 mcg/kg, which is higher than the FDA-recommended starting dose of 1 mcg/kg.

Over half of the patients (51%) achieved a platelet count of ≥50 × 10^9/L by the end of the first week, suggesting that higher initial doses may be effective and safe for improving platelet responses in thrombocytopenic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center. Wong, A., Ahuja, T., Cirrone, F., et al.[2023]

Romiplostim (Nplate) was approved by the US FDA in August 2008 as a treatment for thrombocytopaenia in patients with chronic immune thrombocytopaenic purpura who did not respond adequately to other treatments like corticosteroids, immunoglobulins, or splenectomy.

As a thrombopoietin receptor agonist, romiplostim works by stimulating the production of platelets, which can help improve blood clotting in patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim. Cines, DB., Yasothan, U., Kirkpatrick, P.[2016]

AMG 531 was generally well tolerated in a phase I study with 30 healthy Japanese men, showing safety profiles similar to placebo and only mild treatment-related adverse events reported.

The study demonstrated that AMG 531 effectively increased platelet counts, with significant increases observed in 4 out of 8 subjects at 1 microg/kg and 7 out of 8 at 2 microg/kg, indicating its potential efficacy for treating chronic immune thrombocytopenic purpura.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. Kumagai, Y., Fujita, T., Ozaki, M., et al.[2016]

In a long-term study of 142 patients with chronic immune thrombocytopenic purpura (ITP), romiplostim significantly increased platelet counts in 87% of patients, maintaining effectiveness for up to 156 weeks without tachyphylaxis.

The treatment had an acceptable safety profile, with serious adverse events occurring in 9% of patients, including severe bleeding in 9% and thrombotic events in 5%, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Bussel, JB., Kuter, DJ., Pullarkat, V., et al.[2022]

In two case studies, patients with immune thrombocytopenia experienced stable platelet counts only through continuous weekly dosing of romiplostim, even when their platelet counts exceeded the FDA-recommended threshold of 400k/µL.

This approach of persistent dosing, along with vigilant monitoring, may help prevent dangerous fluctuations in platelet levels, suggesting a potential alternative dosing strategy for romiplostim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic dosing of romiplostim in patients with immune thrombocytopenia purpura: Two case reports. Gilreath, JA., Wei, M., Paul, S., et al.[2019]

Romiplostim (AMG531) effectively increases megakaryocyte proliferation in a dose-dependent manner, as demonstrated in an in vitro study using human cord blood-derived progenitor cells.

The study suggests that the effects of AMG531 on megakaryocyte function are linked to changes in AKT phosphorylation, providing insights into the mechanisms of action for this treatment in immune thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High doses of romiplostim induce proliferation and reduce proplatelet formation by human megakaryocytes. Currao, M., Balduini, CL., Balduini, A.[2021]

In a study of 18 hospitalized patients with severe immune thrombocytopenia, those receiving higher initial doses of romiplostim (≥2 mcg/kg/week) achieved platelet levels of ≥10 × 10^9/L significantly faster (median of 2 days) compared to the standard dose of 1 mcg/kg/week (median of 4.5 days).

Patients on higher doses also had a shorter hospital stay (13.5 days vs. 20 days) and a lower incidence of clinically relevant nonmajor bleeding, suggesting that higher doses may improve treatment outcomes and safety for patients who are refractory to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial romiplostim dosing and time to platelet response in patients with treatment refractory immune thrombocytopenia. DasGupta, RK., Levine, L., Wiczer, T., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Romiplostim. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. [2016]

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

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Dynamic dosing of romiplostim in patients with immune thrombocytopenia purpura: Two case reports. [2019]

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

High doses of romiplostim induce proliferation and reduce proplatelet formation by human megakaryocytes. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Initial romiplostim dosing and time to platelet response in patients with treatment refractory immune thrombocytopenia. [2019]