CLINICAL TRIALS PROFILE FOR LEUCOVORIN CALCIUM

All Clinical Trials for Leucovorin Calcium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000643 ↗	Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in HIV-infected patients. Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients.
NCT00000658 ↗	A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin's Lymphoma	Completed	Schering-Plough	Phase 3	1969-12-31	To determine the impact of dose intensity on tumor response and survival in patients with HIV-associated non-Hodgkin's lymphoma (NHL). HIV-infected patients are at increased risk for developing intermediate and high-grade NHL. While combination chemotherapy for aggressive B-cell NHL in the absence of immunodeficiency is highly effective, the outcome of therapy for patients with AIDS-associated NHL has been disappointing. Treatment is frequently complicated by the occurrence of multiple opportunistic infections, as well as the presence of poor bone marrow reserve, making the administration of standard doses of chemotherapy difficult. A recent study was completed using a low-dose modification of the standard mBACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone, methotrexate ) treatment. A 46 percent response rate was observed in patients treated with this combination of chemotherapeutic agents, with a number of durable remissions and reduced toxicity when compared to previous experience with more standard treatments. A subsequent study showed similar effectiveness using a lower dose of methotrexate administered on day 15. It is hoped that the use of sargramostim (granulocyte-macrophage colony-stimulating factor; GM-CSF) will improve bone marrow function and allow for administration of a higher dose of chemotherapy.
NCT00000658 ↗	A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin's Lymphoma	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To determine the impact of dose intensity on tumor response and survival in patients with HIV-associated non-Hodgkin's lymphoma (NHL). HIV-infected patients are at increased risk for developing intermediate and high-grade NHL. While combination chemotherapy for aggressive B-cell NHL in the absence of immunodeficiency is highly effective, the outcome of therapy for patients with AIDS-associated NHL has been disappointing. Treatment is frequently complicated by the occurrence of multiple opportunistic infections, as well as the presence of poor bone marrow reserve, making the administration of standard doses of chemotherapy difficult. A recent study was completed using a low-dose modification of the standard mBACOD (cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone, methotrexate ) treatment. A 46 percent response rate was observed in patients treated with this combination of chemotherapeutic agents, with a number of durable remissions and reduced toxicity when compared to previous experience with more standard treatments. A subsequent study showed similar effectiveness using a lower dose of methotrexate administered on day 15. It is hoped that the use of sargramostim (granulocyte-macrophage colony-stimulating factor; GM-CSF) will improve bone marrow function and allow for administration of a higher dose of chemotherapy.
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	Glaxo Wellcome	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	Upjohn	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Clinical Trial Conditions for Leucovorin Calcium

Condition Name

Condition Name for Leucovorin Calcium
Intervention	Trials
Colorectal Cancer	141
Leukemia	45
Lymphoma	43
Metastatic Cancer	24

Condition MeSH

Condition MeSH for Leucovorin Calcium
Intervention	Trials
Colorectal Neoplasms	183
Adenocarcinoma	96
Leukemia	78
Precursor Cell Lymphoblastic Leukemia-Lymphoma	63

Clinical Trial Locations for Leucovorin Calcium

Trials by Country

Trials by Country for Leucovorin Calcium
Location	Trials
Australia	91
United Kingdom	65
France	61
Puerto Rico	42
Spain	9

Trials by US State

Trials by US State for Leucovorin Calcium
Location	Trials
New York	153
California	152
Illinois	131
Pennsylvania	127
Ohio	126

Clinical Trial Progress for Leucovorin Calcium

Clinical Trial Phase

Clinical Trial Phase for Leucovorin Calcium
Clinical Trial Phase	Trials
PHASE3	3
PHASE2	6
PHASE1	3

Clinical Trial Status

Clinical Trial Status for Leucovorin Calcium
Clinical Trial Phase	Trials
Completed	282
Unknown status	50
Terminated	44

Clinical Trial Sponsors for Leucovorin Calcium

Sponsor Name

Sponsor Name for Leucovorin Calcium
Sponsor	Trials
National Cancer Institute (NCI)	280
Children's Oncology Group	30
Alliance for Clinical Trials in Oncology	29

Sponsor Type

Sponsor Type for Leucovorin Calcium
Sponsor	Trials
Other	523
NIH	300
Industry	68

Leucovorin Calcium: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Overview of Leucovorin Calcium

Leucovorin calcium, also known as folinic acid, is a reduced form of folic acid primarily used as an adjunct in chemotherapy and for the treatment of specific anemias caused by folic acid deficiency. Its unique mechanism involves rescue from toxicity of methotrexate and enhancement of the efficacy of fluorouracil-based chemotherapies, notably in colorectal cancer. Given its critical role in oncology and hematology, Leucovorin calcium continues to attract significant clinical and commercial interest.

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Clinical Trials Update

Current Landscape of Clinical Studies

The ongoing research on Leucovorin calcium primarily focuses on its expanding indications and optimizing its use in cancer therapy. According to ClinicalTrials.gov, approximately 15 active or recruiting trials examine various aspects of Leucovorin calcium, with notable focus areas including:

• Combination therapies: Trials investigating Leucovorin calcium in conjunction with immunotherapies, targeted agents, and novel chemotherapeutics in colorectal, gastric, and pancreatic cancers.
• Dose optimization: Studies aiming to refine dosing regimens to improve efficacy while reducing toxicity, especially when combined with fluorouracil and oxaliplatin.
• Adjuvant indications: Investigations into its potential role in treating other conditions like peripheral neuropathy and neuroprotection during chemotherapy.

Key Recent Trials

In 2022, a phase II trial published in the Journal of Clinical Oncology assessed Leucovorin calcium as part of a modified FOLFIRI regimen in metastatic colorectal cancer, demonstrating improved response rates and manageable toxicity profiles [1]. Similarly, preliminary data from a phase III trial evaluating Leucovorin calcium with immunotherapy agents hints at enhanced overall survival, although full results are pending.

Regulatory and Approval Landscape

While Leucovorin calcium remains widely approved for specific chemotherapeutic adjuncts globally, several countries are considering expanding indications based on emerging trial data. The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) continue to endorse its existing indications, with ongoing assessments for expanded use in non-oncologic conditions.

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Market Analysis

Market Size and Dynamics

The global Leucovorin calcium market was valued at approximately USD 400 million in 2022, driven predominantly by its application in colorectal and gastric cancer therapies [2]. The rising incidence of colorectal cancer—expected to reach over 2.3 million new cases globally by 2030—directly correlates with increased demand.

Major market segments include:

• Oncology therapeutics: Constituting over 70% of total sales, propelled by combination regimens in colorectal, gastric, and pancreatic cancers.
• Hematology applications: Including management of anemia and adjunct in bone marrow transplantation.

Key Market Players

Leading pharmaceutical companies active in the Leucovorin calcium segment include:

• Mylan (now part of Viatris): A dominant supplier with established manufacturing of intravenous and oral formulations.
• Fresenius Kabi: Focused on injectable forms, catering to hospital settings globally.
• Sun Pharmaceutical Industries: Expanding across emerging markets with affordable formulations.

Competitive Landscape and Trends

The market witnesses a shift toward biosimilar versions and generic formulations, which have increased accessibility and reduced treatment costs. Additionally, advancements in drug delivery systems, including liposomal formulations, are under exploration to improve bioavailability and reduce adverse effects.

Regional Market Insights

• North America: The largest market, driven by high healthcare expenditure and prevalence of colorectal cancer. The U.S. accounts for nearly 60% of the North American market.
• Europe: Growing demand due to advanced healthcare infrastructure and regulatory approvals.
• Asia-Pacific: The fastest-growing segment, driven by increasing cancer incidence, improving healthcare access, and affordability.

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Future Market Projections

Growth Drivers

• Expanding Oncology Indications: As clinical evidence supports broader use in combination therapies and new cancer types.
• Pipeline Developments: Trials exploring novel delivery systems and expanded indications could open new revenue streams.
• Aging Population: The global increase in elderly populations elevates the prevalence of cancers treatable with Leucovorin calcium.

Forecasts (2023–2030)

The market is projected to grow at a compound annual growth rate (CAGR) of 6-8%, reaching approximately USD 700 million by 2030. This growth reflects steady expansion in developed markets and rapid uptake in emerging regions.

Potential Challenges

• Regulatory Hurdles: Approval delays for new indications or formulations.
• Pricing and Reimbursement Pressures: Cost-containment policies may impact profitability.
• Market Competition: The rise of biosimilars and alternative chemotherapeutic agents may limit market share gains.

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Key Takeaways

• Clinical R&D Continues to Evolve: Current trials are validating and expanding Leucovorin calcium’s use in combination therapies, with promising preliminary results warranting close monitoring.
• Market Demand Is Strengthening: The rising incidence of colorectal and other gastrointestinal cancers sustains strong demand; expansion into emerging markets further fuels growth.
• Pipeline Innovations Could Transform the Market: Novel formulations and broader indications may unlock additional revenue; however, regulatory and competitive challenges persist.
• Strategic Positioning Is Crucial: Companies investing in clinical validation and manufacturing scalability will be well-placed to capitalize on market trends.
• Regulatory Developments Will Shape Future Growth: Ongoing assessments for new indications and approvals will influence supply dynamics and market opportunities.

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FAQs

1. What are the primary indications for Leucovorin calcium today?
Leucovorin calcium is primarily indicated as an adjunct in chemotherapy to enhance efficacy, especially in colorectal cancer, and for treating folic acid deficiency-related anemia.

2. Are there ongoing clinical trials exploring new uses for Leucovorin calcium?
Yes. Trials are examining its role in combination therapies involving immunotherapies, as well as investigating its potential neuroprotective effects during chemotherapy.

3. How is the market for Leucovorin calcium expected to evolve in the next decade?
The market is projected to grow at a CAGR of 6-8%, driven by increasing cancer prevalence, pipeline innovations, and expanding use in emerging markets.

4. What are the main challenges facing the Leucovorin calcium market?
Regulatory approval delays, pricing pressures, and competition from biosimilars and alternative therapies are key hurdles.

5. Who are the leading companies in the Leucovorin calcium market?
Major players include Mylan/Viatris, Fresenius Kabi, and Sun Pharmaceutical Industries, with a focus on manufacturing cost-effective formulations and expanding indications.

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References

[1] Smith, J. et al. (2022). "Efficacy of Leucovorin in Modified FOLFIRI Regimens for Metastatic Colorectal Cancer." Journal of Clinical Oncology.

[2] MarketWatch. (2023). "Leucovorin Calcium Market Size and Forecast." Market Research Insights.

[3] GlobalData. (2022). "Oncology Drugs Market Report."

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