Eflapegrastim for Pediatric Cancer

Recruiting at 3 trial locations

Overseen By Howard Franklin, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Spectrum Pharmaceuticals, Inc

Must not be taking: Filgrastim, Pegfilgrastim, G-CSF

Disqualifiers: Uncontrollable infection, Bone marrow transplant, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and metabolism of a new treatment, eflapegrastim, for children with solid tumors or lymphoma who are receiving chemotherapy that reduces blood cell counts. Eflapegrastim is injected after chemotherapy to stimulate white blood cell production. Children and young teenagers diagnosed with solid tumors or lymphoma, without bone marrow cancer, and undergoing chemotherapy may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have used certain drugs like filgrastim or pegfilgrastim recently, and you should not be using investigational drugs or biologics within 30 days before the study.

Is there any evidence suggesting that eflapegrastim is likely to be safe for pediatric cancer patients?

Research shows that eflapegrastim treats neutropenia, a condition characterized by low white blood cell counts due to cancer treatments. However, sufficient information on the safety and effectiveness of eflapegrastim for children is not yet available. While adults have used it, its safety for children remains under study.

This trial is in phase 2, indicating that earlier tests suggested potential safety, but further research is needed to assess how well children tolerate it. Prospective participants should be aware that the researchers are still investigating eflapegrastim’s safety in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Eflapegrastim is unique because it is a long-acting form of the drug, pegfilgrastim, which is commonly used to boost white blood cell counts after chemotherapy. Unlike other treatments that might require more frequent dosing, eflapegrastim is designed for less frequent administration while potentially offering similar or improved effectiveness in enhancing white blood cell recovery. This can be particularly beneficial for young cancer patients who are already undergoing rigorous treatment schedules. Researchers are excited about eflapegrastim because it has the potential to reduce the risk of infections between chemotherapy cycles, making the overall treatment process smoother and more tolerable for pediatric patients.

What evidence suggests that eflapegrastim might be an effective treatment for pediatric cancer?

Research shows that eflapegrastim can lower the risk of febrile neutropenia, a condition where white blood cells drop, causing fever and increasing infection risk, in patients receiving chemotherapy. Studies have found that it helps white blood cells recover faster, which is crucial for fighting infections. In adults with cancers that are not blood-related, eflapegrastim has reduced infection rates. In this trial, participants across various age groups will receive eflapegrastim after each chemotherapy cycle. The treatment supports the immune system, helping patients better tolerate chemotherapy. This makes it a promising option for children with cancer undergoing chemotherapy that affects the bone marrow. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children with solid tumors or lymphoma who are getting strong chemotherapy. They must have a high risk of fever and low white blood cell counts, no bone marrow cancer, good heart function, and be able to do some daily activities. Kids can't join if they've had certain treatments recently, have an infection that's not under control, or are sensitive to drugs similar to Eflapegrastim.

Inclusion Criteria

I will have a lumbar puncture to check for brain or spinal cord involvement if needed.

My heart's pumping ability is good, confirmed by a recent heart scan.

I have a confirmed diagnosis of a new or returning solid tumor or lymphoma without bone marrow involvement.

Exclusion Criteria

I have an active brain or spinal cord disease.

I still experience significant side effects from my previous treatment.

I need radiation therapy during the first treatment cycle.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy as Standard of Care followed by a subcutaneous dose of eflapegrastim up to 4 treatment cycles

Up to 16 weeks

4 cycles, each up to 28 days or more

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events

35 days after the last dose

Long-term follow-up

Participants are monitored for long-term safety and pharmacokinetics

Up to approximately 16 months

What Are the Treatments Tested in This Trial?

Interventions

• Eflapegrastim

Trial Overview The study tests the safety and how the body processes Eflapegrastim in kids receiving chemotherapy that lowers their white blood cells. It aims to see if this drug can help prevent infections by increasing white blood cells after chemo.

How Is the Trial Designed?

Group I: Cohort 4: ≥1 month to <2 years Experimental Treatment 2 Interventions

Participants will receive a SC injection eflapegrastim after completion of each cycle of chemotherapy up to four cycles of treatment (cycle length may vary and can be up to 28 days or more based on the type of chemotherapy regimen selected).

Group II: Cohort 3: ≥2 to <6 years Experimental Treatment 2 Interventions

Participants will receive a SC injection eflapegrastim after completion of each cycle of chemotherapy up to four cycles of treatment (cycle length may vary and can be up to 28 days or more based on the type of chemotherapy regimen selected).

Group III: Cohort 2: ≥6 to <12 years Experimental Treatment 2 Interventions

Participants will receive a SC injection eflapegrastim after completion of each cycle of chemotherapy up to four cycles of treatment (cycle length may vary and can be up to 28 days or more based on the type of chemotherapy regimen selected).

Group IV: Cohort 1: ≥12 to <17 years Experimental Treatment 2 Interventions

Participants will receive a SC injection of eflapegrastim after completion of each cycle of chemotherapy up to four cycles of treatment (cycle length may vary and can be up to 28 days or more based on the type of chemotherapy regimen selected).

Who Is Running the Clinical Trial?

Spectrum Pharmaceuticals, Inc

Lead Sponsor

Trials

83

Recruited

8,200+

Tom Riga

Spectrum Pharmaceuticals, Inc

Chief Executive Officer since 2021

Bachelor's degree in Business Administration from the University of Rhode Island

Francois Lebel

Spectrum Pharmaceuticals, Inc

Chief Medical Officer since 2018

MD from McGill University

Published Research Related to This Trial

Recent studies have shown that therapies targeting the insulin-like growth factor receptor 1 are promising for treating Ewing sarcoma, leading to ongoing clinical trials.

Preclinical investigations are crucial for understanding the effectiveness of new treatments, as some agents, like Src inhibitors, showed no benefit in preventing metastasis in osteosarcoma despite initial promise, highlighting the complexity of pediatric sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents in development for pediatric sarcomas. Hughes, DP.[2018]

The Patient-derived xenograft (PDX) for Childhood Cancer Therapeutics (PCAT) portal provides a comprehensive resource for studying pediatric cancer, featuring 324 PDX models along with clinical and genomic data to aid in the development of new treatments.

PCAT includes curated preclinical testing results for 68 models and 79 therapeutic agents, allowing researchers to identify effective therapies and compare patient tumors with PDX models, enhancing the understanding of pediatric cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCAT: an integrated portal for genomic and preclinical testing data of pediatric cancer patient-derived xenograft models. Yang, J., Li, Q., Noureen, N., et al.[2021]

Olaratumab, a monoclonal antibody targeting PDGFRα, was found to be tolerable and safely administered in a phase 1 trial involving 68 children with relapsed/refractory tumors, showing manageable side effects when combined with standard chemotherapy regimens.

The trial resulted in one complete response and three partial responses among participants, indicating potential efficacy of olaratumab in treating pediatric cancers when used alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of olaratumab monotherapy and in combination with chemotherapy in pediatric patients with relapsed/refractory solid and central nervous system tumors. Mascarenhas, L., Ogawa, C., Laetsch, TW., et al.[2021]

Eflapegrastim, a new long-acting growth factor, was found to be noninferior to pegfilgrastim in reducing the duration of severe neutropenia in patients with early-stage breast cancer, with 20.3% of patients on eflapegrastim experiencing severe neutropenia compared to 23.5% on pegfilgrastim.

Both treatments showed comparable safety profiles, but eflapegrastim was administered at a lower dose of G-CSF, suggesting it may have the potential for improved clinical benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy-induced neutropenia in patients with early-stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): A Phase 3 study. Cobb, PW., Moon, YW., Mezei, K., et al.[2021]

Advancements in treatment for Ewing sarcoma, a common bone cancer in children and young adults, have increased the survival rate from less than 10% to about 60% for patients with localized disease through modern multiagent chemotherapy, radiotherapy, and surgery.

Current standard chemotherapy regimens differ between Europe and North America, with ongoing international trials aimed at improving outcomes for both localized and metastatic Ewing sarcoma, where the 5-year event-free survival rate remains low at 10-30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ewing sarcoma]. Hamanoue, S., Makimoto, A.[2011]

Both sargramostim and filgrastim, colony-stimulating factors used to treat neutropenia, show similar safety profiles, with adverse events occurring at comparable rates to placebo, indicating that the underlying disease may influence side effects more than the drugs themselves.

Due to the lack of clear safety differences between the two drugs, decisions regarding their formulary inclusion should focus on their efficacy and cost rather than solely on safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions. Kellihan, MJ.[2018]

In a study of 72 children with poor prognosis cancers treated on early phase trials over 10 years, dose-limiting toxicities were rare, occurring in only 13% of phase I participants, indicating that these trials are generally safe.

The most common reason for patients leaving trials was disease progression (76%), not drug toxicity, highlighting the need for continued development of novel therapies to improve outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and outcome of children and adolescents participating in phase I/II trials of novel anticancer drugs: the Royal Marsden experience. Morgenstern, DA., Hargrave, D., Marshall, LV., et al.[2022]

In a Phase II study involving 53 children with high-risk medulloblastoma, oral etoposide was found to be tolerable and effective when administered during radiotherapy, leading to a high response rate with 40.4% achieving complete response and 51.1% partial response.

The study reported promising survival rates, with 2-year progression-free survival (PFS) at 76.6% and overall survival (OS) at 80.9%, indicating that this treatment regimen could improve outcomes for children with this aggressive form of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group. Esbenshade, AJ., Kocak, M., Hershon, L., et al.[2018]

The Pediatric MATCH trial, developed by the Children's Oncology Group and the National Cancer Institute, aims to improve outcomes for children with recurrent or refractory cancers by using targeted therapies based on specific genetic mutations, moving away from traditional chemotherapy dose intensification.

The trial will evaluate seven recommended drug-target pairs through a centralized biomarker profiling protocol, indicating a shift towards personalized medicine in pediatric oncology, with a focus on safety and efficacy of these targeted agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial. Allen, CE., Laetsch, TW., Mody, R., et al.[2021]

Recent advances in molecular biology have identified specific tumor targets, such as the EWS-FLI1 fusion protein in Ewing sarcoma and the ETV6-NTRK3 fusion protein in congenital fibrosarcoma, which could lead to more effective and targeted therapies for childhood cancers.

The success of the BCR-ABL kinase inhibitor imatinib mesylate in chronic myeloid leukemia demonstrates the potential of targeting specific molecular pathways to improve treatment outcomes, although challenges like clinical resistance need to be addressed for future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric malignancies provide unique cancer therapy targets. Uren, A., Toretsky, JA.[2019]

Chemotherapy-induced thrombocytopenia (CIT) is a significant issue in Ewing sarcoma treatment, affecting 64% of patients and leading to delays in chemotherapy cycles.

The use of romiplostim, a thrombopoietin receptor agonist, was safe and showed efficacy in increasing platelet counts, with higher doses correlating with greater improvements, indicating its potential to help maintain chemotherapy intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-induced thrombocytopenia in Ewing sarcoma: Implications and potential for romiplostim supportive care. Merjaneh, N., Young, J., Mangoli, A., et al.[2022]

Ewing tumours, which are common malignant bone tumours in children, have a specific chromosomal rearrangement that contributes to their cancerous behavior, and treatments involving multidrug chemotherapy can lead to over 50% long-term survival in localized cases.

Patients with metastases at diagnosis or those who do not respond to initial therapy have a significantly worse prognosis, highlighting the importance of specialized care and the potential benefits of participating in clinical trials for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ewing tumour: incidence, prognosis and treatment options. Paulussen, M., Fröhlich, B., Jürgens, H.[2018]

A study of 235 pediatric patients enrolled in investigational oncology trials showed that these trials are generally safe, with no toxic deaths reported, although 13 patients experienced dose-limiting toxicity, primarily hematologic.

Despite the challenges, 12% of patients had an objective response to treatment, and 16% maintained stable disease for over 4 months, indicating that phase I to II trials can provide clinical benefits and are valuable in managing relapsed cancer in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients in pediatric phase I and early phase II clinical oncology trials at Gustave Roussy: a 13-year center experience. Bautista, F., Di Giannatale, A., Dias-Gastellier, N., et al.[2015]

Plerixafor was successfully used to mobilize stem cells in a 14-year-old girl with Ewing's sarcoma after previous treatments failed to do so with G-CSF alone or in combination with chemotherapy.

No side effects were observed during the use of plerixafor, suggesting it may be a safe option for stem cell collection in pediatric patients with solid tumors, although further studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor plus G-CSF in combination with chemotherapy for stem cell mobilization in a pediatric patient with Ewing's sarcoma. Vives, S., Sancho, JM., Almazán, F., et al.[2021]

Eflapegrastim is a safe and well-tolerated treatment for reducing chemotherapy-induced neutropenia, showing no significant adverse events in a study of 84 healthy participants, including both Japanese and Caucasian subjects.

The drug demonstrated a dose-dependent increase in both the maximum serum concentration and the absolute neutrophil count, indicating its efficacy in boosting immune response, with similar pharmacokinetic and pharmacodynamic profiles across different ethnic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo- and Active-Controlled, Escalating Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Profiles of Subcutaneous Eflapegrastim in Healthy Japanese and Caucasian Subjects. Jeon, Y., Lee, N., Baek, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03135951

Pharmacokinetics of SPI-2012 (Eflapegrastim) in Breast ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761148Orig1s000MedR.pdf

761148Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov The analyses of all secondary efficacy endpoints including time to ANC recovery, depth of ANC nadir, and incidence of febrile neutropenia also showed that there ...

3. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6e436115-62e7-4729-aeb0-ff78ea685206

ROLVEDON- eflapegrastim-xnst injection, solution - DailyMed Rolvedon is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01724866?cond=Breast%20Cancer&distance=50&term=HM10460A&rank=2

Phase 2 Study of SPI-2012 or Pegfilgrastim for the ... The purpose of this study is to assess the effect of test doses of SPI-2012 on the duration of severe neutropenia (DSN) during Cycle 1 in participants with ...

5. reference.medscape.com reference.medscape.com/drug/rolvedon-eflapegrastim-4000053

Rolvedon (eflapegrastim) dosing, indications, interactions, ... Indicated to decrease incidence of infection, as manifested by febrile neutropenia, in adults with non-myeloid malignancies receiving myelosuppressive ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/eflapegrastim-xnst-subcutaneous-route/description/drg-20538808

Eflapegrastim-xnst (subcutaneous route) - Side effects & ... Eflapegrastim-xnst injection is used to treat neutropenia (low white blood cells) that is caused by cancer medicines.

7. rolvedon.com rolvedon.com/pdf/rolvedon-prescribing-information.pdf

Rolvedon™ prescribing information 8.4 Pediatric Use. Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use. Of the 314 patients in clinical studies of ...

8. drugs.com drugs.com/cons/eflapegrastim-xnst.html

Eflapegrastim-xnst Advanced Patient Information ... eflapegrastim-xnst injection in the pediatric population. Safety and efficacy have not been established. Geriatric. Appropriate studies ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761148Orig1s000CrossR.pdf

761148Orig1s000 - accessdata.fda.gov At this time, the safety and efficacy eflapegrastim-xnst have not been established in pediatric patients. 7. Advisory Committee Meeting and ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04570423

NCT04570423 | A Study to Evaluate the Safety and ... The purpose of this study is to evaluate the safety and pharmacokinetics of eflapegrastim in pediatric participants with solid tumors or lymphoma and treated ...