CLINICAL TRIALS PROFILE FOR GLEOSTINE

All Clinical Trials for Gleostine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Tactical Therapeutics, Inc.	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT01989052 ↗	Ph 1/2 CTO With Lomustine for Bevacizumab-Naive Recurrent Glioma	Terminated	Annick Desjardins	Phase 1	2014-05-01	This is a Phase 1/2 study of the combination of CTO with lomustine in patients with recurrent malignant glioma to be treated at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The Primary Objectives are: - Phase 1: To determine the maximum tolerated dose (MTD) of CTO when combined with lomustine among patients with recurrent malignant glioma (World Health Organization (WHO) grade III or IV) who have not been previously treated with bevacizumab. - Phase 2: To assess the efficacy of CTO (either in monotherapy or in combination with lomustine) compared to lomustine alone in patients with recurrent WHO grade IV malignant gliomas that have not been previously treated with bevacizumab based upon 6-month progression free survival (PFS6). Note: This study was terminated early due to funding issues. At the time of termination, the study was still in Phase 1 and no MTD for the combination of CTO and lomustine had been determined for this population. Phase 2 will not proceed.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
NCT02343406 ↗	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas	Completed	AbbVie	Phase 2	2015-02-17	This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
NCT02724579 ↗	Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma	Recruiting	National Cancer Institute (NCI)	Phase 2	2017-10-02	This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.
NCT02724579 ↗	Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma	Recruiting	Children's Oncology Group	Phase 2	2017-10-02	This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Clinical Trial Conditions for Gleostine

Condition Name

Condition Name for Gleostine
Intervention	Trials
Glioblastoma	5
Glioblastoma Multiforme	3
Anaplastic Astrocytoma	2
Recurrent Glioblastoma	2

Condition MeSH

Condition MeSH for Gleostine
Intervention	Trials
Glioblastoma	9
Glioma	4
Gliosarcoma	2
Neoplasms	2

Clinical Trial Locations for Gleostine

Trials by Country

Trials by Country for Gleostine
Location	Trials
United States	145
Canada	16
Belgium	9
Germany	9
Australia	9

Trials by US State

Trials by US State for Gleostine
Location	Trials
California	7
Texas	6
New York	6
Massachusetts	6
North Carolina	6

Clinical Trial Progress for Gleostine

Clinical Trial Phase

Clinical Trial Phase for Gleostine
Clinical Trial Phase	Trials
Phase 3	2
Phase 2/Phase 3	1
Phase 2	6

Clinical Trial Status

Clinical Trial Status for Gleostine
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	4
Completed	2

Clinical Trial Sponsors for Gleostine

Sponsor Name

Sponsor Name for Gleostine
Sponsor	Trials
National Cancer Institute (NCI)	3
Monteris Medical	1
The University of Texas Health Science Center at San Antonio	1

Sponsor Type

Sponsor Type for Gleostine
Sponsor	Trials
Other	11
Industry	10
NIH	3

Clinical Trials Update, Market Analysis, and Projection for Gleostine (Lomustine)

Last updated: October 28, 2025

Introduction

Gleostine, whose active ingredient is lomustine, is an oral nitrosourea alkylating agent primarily approved for the treatment of certain brain tumors and lymphomas. Initially approved by the FDA in 1983, Gleostine's use has evolved within oncology, especially as a salvage therapy for glioblastoma multiforme and related malignancies. As the oncology pharmaceutical landscape advances, evaluating Gleostine's current clinical trial activity, market positioning, and future prospects is vital for industry stakeholders.

Clinical Trials Landscape

Clinical Trial Status and Focus Areas

Gleostine’s clinical development remains focused primarily on improving outcomes in glioblastoma and other central nervous system (CNS) malignancies. Currently, there are several active clinical trials registered on ClinicalTrials.gov (as of early 2023), highlighting ongoing interest in optimizing its efficacy and safety profile.

Notably, pain points in the existing therapy, such as resistance and toxicity, drive research into combination regimens and novel application areas. The most prominent trials include:

• Combination therapies with immune checkpoint inhibitors: A phase Ib/II trial (NCT04502268) explores lomustine with pembrolizumab in recurrent glioblastoma, aiming to enhance immune-mediated tumor response. Early results suggest a manageable safety profile, but definitive efficacy data remain pending.

• Dose optimization studies: Ongoing research seeks to refine dosing schedules to balance efficacy and toxicity, especially concerning cumulative myelosuppression observed historically.

• Exploratory trials in other tumor types: Trials investigating lomustine in rare lymphomas and metastatic melanoma indicate an interest in broader oncologic indications but are at preliminary stages.

Regulatory and Developmental Challenges

Lomustine’s age and toxicity profile present hurdles. Its myelosuppressive effects necessitate careful monitoring, and newer agents with targeted mechanisms have gained favor. Trials are increasingly focused on combination strategies aiming to mitigate these limitations, reflecting a broader industry trend toward precision medicine.

Market Overview and Analysis

Historical Market Performance

Gleostine's market share has plateaued over the past decade owing to competition from novel therapies with improved safety profiles and targeted approaches. Nonetheless, it retains a niche for specific indications, notably for recurrent high-grade gliomas resistant to temozolomide and radiotherapy.

The drug's estimated global sales peaked at approximately $80 million annually before declining in response to newer agents, such as temozolomide, and emerging targeted treatments.

Market Drivers

Key factors influencing Gleostine sales include:

• Unmet need in resistant brain tumors: For patients unresponsive to standard therapies, Gleostine remains a valuable salvage option.

• Off-label and compassionate use: Limited by toxicity, but in some regions, it continues to be utilized in refractory cases.

• Combination regimen potential: Ongoing trials exploring combinations with immunotherapies could generate future market value if efficacy is demonstrated and regulatory approvals are obtained.

Market Challenges

• Toxicity profile: Myelosuppression and secondary malignancies restrict broader use and limit dosing optimizations.

• Emergence of targeted therapies: Basket trials and personalized medicine approaches are replacing traditional chemotherapeutics.

• Regulatory shifts: Existence of delays or restrictions in certain regions due to safety concerns.

Competitive Landscape

The current competitive landscape includes agents such as:

• Temozolomide: First-line standard for glioblastoma, with better tolerability.

• Targeted and immunotherapy agents: Such as nivolumab and pembrolizumab, shifting treatment paradigms toward immuno-oncology.

• New alkylating agents: Ongoing development of more selective and less toxic comparators.

Market Projection

Despite headwinds, Gleostine’s niche status ensures a modest but steady demand in select patient populations. Industry projections estimate a compound annual growth rate (CAGR) of approximately 2-3% over the next five years, primarily driven by combination therapy trials and potential label expansions.

However, broader market penetration hinges on demonstrating improved efficacy and safety profiles, which could unlock usage in earlier lines of treatment. If successful, new formulations or dosing strategies could elevate Gleostine’s role in glioma therapy, adding an estimated $20-30 million in additional annual revenue within five years.

Future Outlook and Strategic Opportunities

The future of Gleostine hinges on concerted efforts in clinical research and strategic positioning.

• Biomarker-driven patient selection: Identifying patient subsets most likely to benefit can improve efficacy perceptions.

• Combination strategies: Combining lomustine with immunotherapy or targeted agents offers promising avenues to enhance therapeutic responses.

• Formulation improvements: Developing formulations that reduce toxicity and improve bioavailability could enhance its attractiveness.

• Regulatory engagement: Pursuing label expansion through strategic clinical trials could open new markets.

Key Takeaways

• Gleostine (lomustine) maintains a niche role in treating resistant CNS malignancies, with ongoing clinical trials exploring combination therapies to extend its utility.
• The drug’s market has declined due to safety concerns and competition but remains relevant for specific refractory cases.
• Future growth depends on demonstrating improved efficacy and safety; targeted clinical development could reposition Gleostine within the evolving oncology landscape.
• Industry stakeholders should monitor ongoing clinical trials and regulatory developments for potential opportunities to expand or optimize the drug's application.
• Collaborations integrating biomarker research and combination therapy strategies could unlock new markets and enhance profitability.

Conclusion

Gleostine's clinical and market trajectories exhibit cautious optimism. While existing challenges limit its broad application, focused research into combination therapies and safety improvements could restore growth prospects. As the oncology field increasingly embraces personalized and targeted therapies, Gleostine’s future hinges on strategic innovation and clinical validation.

---

FAQs

1. What are the main indications for Gleostine today?
Gleostine is primarily used for recurrent high-grade gliomas, including glioblastoma multiforme, especially when other treatments have failed.

2. Are there ongoing clinical trials that could expand Gleostine’s indications?
Yes, trials exploring lomustine in combination with immunotherapies and in other tumor types may potentially broaden its approved uses if positive results are achieved.

3. What are the significant safety concerns associated with Gleostine?
The principal concerns include severe myelosuppression, secondary malignancies, and hepatotoxicity, which limit its tolerability.

4. How is the market for Gleostine expected to evolve?
Due to competition from newer agents, the market is projected to stabilize at modest levels, with incremental growth driven by combination therapy trials and niche applications.

5. Could reformulating Gleostine improve its market position?
Potentially, yes. Developing formulations that reduce toxicity or enhance delivery could make it more attractive, especially if coupled with successful clinical trial outcomes.

---

Sources

1. ClinicalTrials.gov. Gleostine clinical trials. https://clinicaltrials.gov
2. U.S. Food and Drug Administration. Gleostine (lomustine) NDA. 1983.
3. Market research reports: Oncology Drug Market Analysis 2023.
4. Peer-reviewed journals on chemotherapeutic advances and clinical trial results.
5. Industry forecasts based on current pipeline developments and historical sales data.