CLINICAL TRIALS PROFILE FOR THALIDOMIDE

505(b)(2) Clinical Trials for THALIDOMIDE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT00116961 ↗	Velcade, Doxil, and Dexamethasone (VDd) as First Line Therapy for Multiple Myeloma	Completed	University of Michigan Cancer Center	Phase 2	2005-06-01	This is a research study for patients with newly diagnosed multiple myeloma. Multiple myeloma remains a non-curable disease however, newer medications and their combinations appear to provide higher response rates and higher complete response rates than current treatment options. One of the new medications in multiple myeloma is Velcade. Preliminary results from a study using a combination of Velcade with Doxil have shown high response rates (disease reduction). Preliminary results also show that an addition of dexamethasone to Velcade in patients not responding to Velcade alone showed improved response rates. This study involves treatment with a new combination of three standard medications: Velcade, Doxil, and dexamethasone (VDd combination). The proposed combination of all three drugs may improve efficacy and response. Velcade is approved by the Food and Drug Administration (FDA) for treatment in multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Velcade is still currently under investigation for other indications. Doxil is not approved for use in multiple myeloma but is an approved drug for use in patients with some other cancers. Several published clinical trials provide evidence that Doxil is an active agent in multiple myeloma and it is used in treatment combinations for multiple myeloma in general practice. Dexamethasone is a standard therapy for multiple myeloma, but is not approved by the FDA for that use. The combination of all three drugs is experimental (not FDA approved). The goals of this study are to determine if this new combination therapy with Velcade, Doxil and dexamethasone is an effective treatment and also to determine the side effects that occur when this combination treatment is given.
New Combination	NCT00116961 ↗	Velcade, Doxil, and Dexamethasone (VDd) as First Line Therapy for Multiple Myeloma	Completed	University of Michigan Rogel Cancer Center	Phase 2	2005-06-01	This is a research study for patients with newly diagnosed multiple myeloma. Multiple myeloma remains a non-curable disease however, newer medications and their combinations appear to provide higher response rates and higher complete response rates than current treatment options. One of the new medications in multiple myeloma is Velcade. Preliminary results from a study using a combination of Velcade with Doxil have shown high response rates (disease reduction). Preliminary results also show that an addition of dexamethasone to Velcade in patients not responding to Velcade alone showed improved response rates. This study involves treatment with a new combination of three standard medications: Velcade, Doxil, and dexamethasone (VDd combination). The proposed combination of all three drugs may improve efficacy and response. Velcade is approved by the Food and Drug Administration (FDA) for treatment in multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Velcade is still currently under investigation for other indications. Doxil is not approved for use in multiple myeloma but is an approved drug for use in patients with some other cancers. Several published clinical trials provide evidence that Doxil is an active agent in multiple myeloma and it is used in treatment combinations for multiple myeloma in general practice. Dexamethasone is a standard therapy for multiple myeloma, but is not approved by the FDA for that use. The combination of all three drugs is experimental (not FDA approved). The goals of this study are to determine if this new combination therapy with Velcade, Doxil and dexamethasone is an effective treatment and also to determine the side effects that occur when this combination treatment is given.
New Combination	NCT02188368 ↗	Pomalidomide for Lenalidomide for Relapsed or Refractory Multiple Myeloma Patients	Active, not recruiting	Celgene Corporation	Phase 2	2014-08-01	The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of pomalidomide given as part of a combination therapy that include more than just steroids to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM). Pomalidomide (alone or in combination with dexamethasone) has been approved by the United States Food and Drug Administration (FDA) for the treatment of MM patients who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of their last therapy. However, the use of pomalidomide in combination with other drugs used to treat MM, such as chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere with the development of small blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. The testing done with pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM both on its own and in combination with dexamethasone. Using another drug class, namely proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with another in an established anti-myeloma treatment regimen can frequently overcome resistance regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the toxicity profile of the new combinations closely resembled that of the proteasome inhibitor administered as a single agent. Based on this experience, we hypothesize that the replacement of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory MM patient population.
New Combination	NCT02188368 ↗	Pomalidomide for Lenalidomide for Relapsed or Refractory Multiple Myeloma Patients	Active, not recruiting	Oncotherapeutics	Phase 2	2014-08-01	The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of pomalidomide given as part of a combination therapy that include more than just steroids to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM). Pomalidomide (alone or in combination with dexamethasone) has been approved by the United States Food and Drug Administration (FDA) for the treatment of MM patients who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of their last therapy. However, the use of pomalidomide in combination with other drugs used to treat MM, such as chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere with the development of small blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. The testing done with pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM both on its own and in combination with dexamethasone. Using another drug class, namely proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with another in an established anti-myeloma treatment regimen can frequently overcome resistance regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the toxicity profile of the new combinations closely resembled that of the proteasome inhibitor administered as a single agent. Based on this experience, we hypothesize that the replacement of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory MM patient population.

All Clinical Trials for THALIDOMIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000790 ↗	Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection	Completed	Andrulis Pharmaceuticals	Phase 2	1969-12-31	PRIMARY: To evaluate the effectiveness and safety of thalidomide for treatment of oral and esophageal aphthous ulcers (those unrelated to a known infection or malignancy) in patients with advanced HIV disease. To evaluate the effect of thalidomide on HIV load in this patient population. Per 06/28/94 amendment, to evaluate the effectiveness of thalidomide in preventing recurrences in patients whose aphthae completely heal at the end of acute treatment. SECONDARY: To evaluate the effect of thalidomide on blood tumor necrosis factor (TNF) levels and to obtain pharmacokinetic data on the drug. Per 06/28/94 amendment, to evaluate the safety of thalidomide. Per 05/10/95 amendment, to explore in a substudy the effects of thalidomide on idiopathic genital aphthous ulcers in HIV-infected women. Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients.
NCT00000790 ↗	Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	PRIMARY: To evaluate the effectiveness and safety of thalidomide for treatment of oral and esophageal aphthous ulcers (those unrelated to a known infection or malignancy) in patients with advanced HIV disease. To evaluate the effect of thalidomide on HIV load in this patient population. Per 06/28/94 amendment, to evaluate the effectiveness of thalidomide in preventing recurrences in patients whose aphthae completely heal at the end of acute treatment. SECONDARY: To evaluate the effect of thalidomide on blood tumor necrosis factor (TNF) levels and to obtain pharmacokinetic data on the drug. Per 06/28/94 amendment, to evaluate the safety of thalidomide. Per 05/10/95 amendment, to explore in a substudy the effects of thalidomide on idiopathic genital aphthous ulcers in HIV-infected women. Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients.
NCT00000812 ↗	A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection	Completed	Celgene Corporation	Phase 1	1969-12-31	PRIMARY: To evaluate the safety, tolerability, and pharmacokinetics of daily oral thalidomide. SECONDARY: To examine the effect of thalidomide on antiviral activity and tumor necrosis factor-alpha (TNF-alpha) production, and the correlation between TNF-alpha inhibition and viral burden. A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.
NCT00000812 ↗	A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	PRIMARY: To evaluate the safety, tolerability, and pharmacokinetics of daily oral thalidomide. SECONDARY: To examine the effect of thalidomide on antiviral activity and tumor necrosis factor-alpha (TNF-alpha) production, and the correlation between TNF-alpha inhibition and viral burden. A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.
NCT00001446 ↗	A Randomized Phase II Study of Oral Thalidomide in Patients With Hormone-Refractory Prostate Cancer	Completed	National Cancer Institute (NCI)	Phase 2	1995-09-01	This is a phase II study designed to evaluate the potential clinical efficacy of thalidomide in patients with hormone-refractory prostate cancer. An important aspect of this study is to characterize the pharmacokinetics of thalidomide, as well as make correlations between the degree of angiogenesis occurring in a patient and the activity of thalidomide.

Clinical Trial Conditions for THALIDOMIDE

Condition Name

Condition Name for THALIDOMIDE
Intervention	Trials
Multiple Myeloma	151
Multiple Myeloma and Plasma Cell Neoplasm	19
Leukemia	9
Myeloma	9

Condition MeSH

Condition MeSH for THALIDOMIDE
Intervention	Trials
Multiple Myeloma	197
Neoplasms, Plasma Cell	187
Lymphoma	29
Plasmacytoma	22

Clinical Trial Locations for THALIDOMIDE

Trials by Country

Trials by Country for THALIDOMIDE
Location	Trials
United States	949
China	117
Canada	55
Italy	53
United Kingdom	44

Trials by US State

Trials by US State for THALIDOMIDE
Location	Trials
New York	79
California	45
Texas	45
Ohio	45
Arkansas	41

Clinical Trial Progress for THALIDOMIDE

Clinical Trial Phase

Clinical Trial Phase for THALIDOMIDE
Clinical Trial Phase	Trials
PHASE4	2
PHASE3	3
PHASE2	13

Clinical Trial Status

Clinical Trial Status for THALIDOMIDE
Clinical Trial Phase	Trials
Completed	271
Unknown status	76
Terminated	64

Clinical Trial Sponsors for THALIDOMIDE

Sponsor Name

Sponsor Name for THALIDOMIDE
Sponsor	Trials
National Cancer Institute (NCI)	100
Celgene Corporation	75
University of Arkansas	30

Sponsor Type

Sponsor Type for THALIDOMIDE
Sponsor	Trials
Other	716
Industry	194
NIH	122

Thalidomide: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Introduction

Thalidomide, once notorious for its teratogenic effects in the 1950s and 1960s, has experienced a significant transformation in its medical application. Originally marketed as a sedative and antiemetic, thalidomide was withdrawn due to birth defect scandals. However, advances in pharmacology and controlled clinical use have repositioned the drug, particularly in oncology and immunology. This comprehensive analysis provides an update on recent clinical trials, market trends, and future projections for thalidomide, aiming to inform industry professionals and stakeholders.

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Recent Clinical Trials and Therapeutic Repositioning

1. Clinical Trial Landscape Overview

Recent years have seen a surge in clinical trials exploring the efficacy of thalidomide and its derivatives (notably lenalidomide and pomalidomide) in various indications, particularly multiple myeloma, leprosy-related conditions, and certain inflammatory disorders.

2. Multiple Myeloma and Oncology Applications

Thalidomide remains a cornerstone in multiple myeloma treatment protocols, prominently in combination therapies. The FDA-approved Thalomid (thalidomide) was first authorized in 2006, with ongoing trials refining dosage and combination regimens. Notably, Phase III trials such as the MM-003 study demonstrated improved progression-free survival (PFS) with thalidomide-based regimens in relapsed/refractory multiple myeloma (R/R MM).

Emerging studies are evaluating the synergistic effects of thalidomide with proteasome inhibitors (e.g., bortezomib) and monoclonal antibodies (e.g., daratumumab), aiming to enhance response rates (NCT identifiers: NCT03151862, NCT03584161).

3. Leprosy and Infectious Disease

Thalidomide’s immunomodulatory properties are exploited in treating erythema nodosum leprosum (ENL), a complication of leprosy. Recent trials reaffirm its efficacy, with studies like the LEPROSY trial demonstrating rapid symptom control. Its role remains vital in certain developing countries with high leprosy prevalence.

4. Other Indications Under Investigation

Preliminary trials are exploring thalidomide’s potential in treating vasculitis, graft-versus-host disease (GVHD), and certain autoimmune conditions. However, these are in early phases, with limited data yet.

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Market Analysis

1. Market Size and Growth Drivers

The global thalidomide market is driven by increased adoption in multiple myeloma, multiple myeloma-related indications, and niche autoimmune diseases. The market was valued at approximately USD 260 million in 2022, with a compound annual growth rate (CAGR) of ~7% projected until 2028 (research from MarketWatch). This growth hinges on:

• Expanding indications for thalidomide and its derivatives.
• Increasing prevalence of multiple myeloma, notably in aging populations.
• Rising adoption of oral chemotherapy agents.

2. Geographical Market Dynamics

North America dominates due to advanced healthcare infrastructure, regulatory approval, and clinical adoption. The U.S. accounts for roughly 60% of sales, supported by FDA approvals and insurance reimbursement policies.

In Europe, growing awareness and availability of alternatives bolster market penetration. The Asia-Pacific region represents significant growth potential due to high leprosy prevalence, economic growth, and expanding healthcare access, especially in India and Southeast Asia.

3. Regulatory and Patent Landscape

Regulatory agencies continue to authorize thalidomide for specific indications, with orphan drug designations aiding market exclusivity. Originator firms like Celgene (now a Bristol-Myers Squibb subsidiary) hold key patents, although some have expired or are nearing expiry, opening avenues for biosimilars and generics.

4. Competitive Landscape

Market players include Celgene/Bristol-Myers Squibb, Teva Pharmaceutical Industries, and Natco Pharma. The development pipeline emphasizes next-generation derivatives with improved safety profiles, aiming to mitigate teratogenic risks—a principal concern.

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Future Market Projections

1. Short to Mid-term Outlook (2023-2028)

• Market Expansion: The market is poised for steady growth owing to ongoing clinical trial success and increasing adoption in oncology.
• Product Development: Introduction of safer, more targeted derivatives, including immunomodulatory agents with reduced teratogenicity, will likely expand indications.
• Regulatory Approvals: Additional approvals for new formulations and combinatorial regimens are anticipated, further consolidating market share.

2. Long-term Outlook (2028 and beyond)

• Diversification of Indications: Promising data on autoimmune and inflammatory diseases could unlock new markets.
• Genomic and Precision Medicine: Biomarker-driven patient selection may optimize efficacy, reducing adverse events and broadening the use-case spectrum.
• Market Challenges: Safety concerns persist, notably teratogenicity, necessitating rigorous patient management protocols which might limit widespread use.

3. Impact of Biosimilars and Generic Competition

The expiration of key patents will foster competitive pressures. Biosimilar versions are expected within the next 3-5 years, likely decreasing prices and expanding access, especially in emerging markets.

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Key Challenges and Opportunities

• Safety Management: Ensuring stringent pregnancy prevention programs is essential to prevent teratogenic risks.
• Regulatory Hurdles: Variations across jurisdictions may slow expansion into new indications.
• Innovative Derivatives: Developing next-generation compounds with improved safety profiles offers lucrative opportunities.
• Patient Stratification: Enhanced genomics-based approaches could improve targeted therapy, reducing adverse effects.

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Key Takeaways

• Clinical resurgence: Thalidomide’s repositioning is primarily driven by its efficacy in multiple myeloma and immune disorders, supported by ongoing clinical trials exploring combination therapies and new indications.
• Market stability and growth: The global market reflects moderate but steady expansion, bolstered by increasing demand in developed regions and significant growth potential in emerging markets.
• Regulatory dynamics: Patent expirations and upcoming biosimilar approvals will influence pricing and market access strategies.
• Safety as a priority: Managing teratogenic risks remains paramount; innovations aimed at safety enhancement will determine future adoption.
• Pipeline potential: The development pipeline offers opportunities for newer, safer analogs, potentially transforming therapeutic landscapes and expanding global usage.

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FAQs

Q1: What are the primary therapeutic indications for thalidomide today?
A: Today, thalidomide is chiefly used for multiple myeloma, erythema nodosum leprosum (ENL), and certain inflammatory conditions, thanks to its immunomodulatory properties.

Q2: How do new derivatives like lenalidomide compare with traditional thalidomide?
A: Lenalidomide offers improved efficacy and a better safety profile, notably reduced peripheral neuropathy and teratogenicity. It is often preferred in current treatment protocols.

Q3: What safety protocols are in place to prevent thalidomide’s teratogenic risks?
A: Strict pregnancy prevention programs—including patient counseling, pregnancy testing, and regulatory oversight—are mandatory for prescription and distribution.

Q4: What is the outlook for biosimilars and generics in the thalidomide market?
A: As patent protections expire, biosimilar versions are expected to enter the market within 3-5 years, heightening competition and reducing costs.

Q5: Which emerging indications could expand thalidomide’s market in the future?
A: Promising areas include autoimmune diseases, graft-versus-host disease (GVHD), and vasculitis, pending successful clinical trial results.

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Sources

[1] MarketWatch. (2022). Thalidomide Market Size and Growth Analysis.
[2] ClinicalTrials.gov. Database of current clinical trials involving thalidomide.
[3] FDA. Thalomid drug approval documentation and safety guidelines.
[4] Jain, T. et al. (2022). Advances in Thalidomide Derivatives for Oncology. Journal of Hematology.
[5] WHO. Leprosy treatment guidelines and drug use.

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Conclusion

Thalidomide’s journey from a banned drug to a therapeutic mainstay exemplifies cautious repurposing driven by rigorous clinical evaluation. Its future hinges on balancing therapeutic benefits with safety challenges, especially teratogenic risks. Market growth prospects are favorable, supported by ongoing clinical development, expanding indications, and biosimilar entries. Stakeholders should focus on innovation, regulatory compliance, and safety management to capitalize on the evolving landscape of thalidomide therapeutics.