CLINICAL TRIALS PROFILE FOR CYTARABINE; DAUNORUBICIN

505(b)(2) Clinical Trials for CYTARABINE; DAUNORUBICIN

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 Formulation	NCT04992949 ↗	Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm	Not yet recruiting	Acute Leukemia French Association	Phase 2	2021-10-01	The three classic myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The natural history of these MPNs is the possible progression to acute myeloid leukemia (MPN-blast phase) at variable percentage depending the entity. Leukemic transformation of MPN occurs in 8% to 23% of primary myelofibrosis (PMF) patients in the first 10 years after diagnosis and in 4% to 8% of polycythemia vera (PV) and essential thrombocytosis (ET) patients within 18 years after diagnosis. The risk for leukemic transformation is increased by exposure to cytotoxic chemotherapy. The molecular pathogenesis of MPN-blast phase remains an area of active research. The prognosis of blast phase MPNs is very poor : approximately 50% of the patients are deemed eligible for intensive treatment (ie. conventional induction chemotherapy regimen with anthracyclines and cytarabine). The patients who are not fit for such intensive treatment approach due to age or comorbidities, are treated with Hypomethylating agents, low dose palliative chemotherapy, or supportive care. Nevertheless, there is a need for more effective and better tolerated treatment approaches in order to increase the response rate and hence, the transplant rates which should translate into improved survival. CPX-351 is a new formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar-ratio in liposomes that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. Based on similarities between post-myelodysplastic syndrome (MDS) and post-MPN secondary AML in terms of disease resistance to chemotherapy, of fragile patient profile, The hypotheses made is that CPX-351 may improve the results of induction chemotherapy without increasing its toxicity and therefore may increase the proportion of patients who could benefit from an allogeneic Stem Cell Transplantation (SCT).
New Formulation	NCT04992949 ↗	Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm	Not yet recruiting	French Intergroup of Myeloproliferative syndromes	Phase 2	2021-10-01	The three classic myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The natural history of these MPNs is the possible progression to acute myeloid leukemia (MPN-blast phase) at variable percentage depending the entity. Leukemic transformation of MPN occurs in 8% to 23% of primary myelofibrosis (PMF) patients in the first 10 years after diagnosis and in 4% to 8% of polycythemia vera (PV) and essential thrombocytosis (ET) patients within 18 years after diagnosis. The risk for leukemic transformation is increased by exposure to cytotoxic chemotherapy. The molecular pathogenesis of MPN-blast phase remains an area of active research. The prognosis of blast phase MPNs is very poor : approximately 50% of the patients are deemed eligible for intensive treatment (ie. conventional induction chemotherapy regimen with anthracyclines and cytarabine). The patients who are not fit for such intensive treatment approach due to age or comorbidities, are treated with Hypomethylating agents, low dose palliative chemotherapy, or supportive care. Nevertheless, there is a need for more effective and better tolerated treatment approaches in order to increase the response rate and hence, the transplant rates which should translate into improved survival. CPX-351 is a new formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar-ratio in liposomes that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. Based on similarities between post-myelodysplastic syndrome (MDS) and post-MPN secondary AML in terms of disease resistance to chemotherapy, of fragile patient profile, The hypotheses made is that CPX-351 may improve the results of induction chemotherapy without increasing its toxicity and therefore may increase the proportion of patients who could benefit from an allogeneic Stem Cell Transplantation (SCT).
New Formulation	NCT04992949 ↗	Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm	Not yet recruiting	French Innovative Leukemia Organisation	Phase 2	2021-10-01	The three classic myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The natural history of these MPNs is the possible progression to acute myeloid leukemia (MPN-blast phase) at variable percentage depending the entity. Leukemic transformation of MPN occurs in 8% to 23% of primary myelofibrosis (PMF) patients in the first 10 years after diagnosis and in 4% to 8% of polycythemia vera (PV) and essential thrombocytosis (ET) patients within 18 years after diagnosis. The risk for leukemic transformation is increased by exposure to cytotoxic chemotherapy. The molecular pathogenesis of MPN-blast phase remains an area of active research. The prognosis of blast phase MPNs is very poor : approximately 50% of the patients are deemed eligible for intensive treatment (ie. conventional induction chemotherapy regimen with anthracyclines and cytarabine). The patients who are not fit for such intensive treatment approach due to age or comorbidities, are treated with Hypomethylating agents, low dose palliative chemotherapy, or supportive care. Nevertheless, there is a need for more effective and better tolerated treatment approaches in order to increase the response rate and hence, the transplant rates which should translate into improved survival. CPX-351 is a new formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar-ratio in liposomes that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. Based on similarities between post-myelodysplastic syndrome (MDS) and post-MPN secondary AML in terms of disease resistance to chemotherapy, of fragile patient profile, The hypotheses made is that CPX-351 may improve the results of induction chemotherapy without increasing its toxicity and therefore may increase the proportion of patients who could benefit from an allogeneic Stem Cell Transplantation (SCT).

All Clinical Trials for CYTARABINE; DAUNORUBICIN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00002471 ↗	Combination Chemotherapy in Treating Patients With Acute B-Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma	Completed	Memorial Sloan Kettering Cancer Center	Phase 2	1990-02-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have acute B-lymphoblastic leukemia or recurrent non-Hodgkin's lymphoma.
NCT00002499 ↗	Combination Chemotherapy in Treating Children With Relapsed Acute Lymphocytic Leukemia	Unknown status	Grupo Argentino de Tratamiento de la Leucemia Aguda	Phase 2/Phase 3	1990-01-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II/III trial to study the effectiveness of combination chemotherapy in treating children with relapsed acute lymphocytic leukemia.
NCT00002514 ↗	Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission	Completed	Medical Research Council	Phase 3	1993-04-01	RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission.
NCT00002514 ↗	Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission	Completed	National Cancer Institute (NCI)	Phase 3	1993-04-01	RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission.
NCT00002514 ↗	Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission	Completed	Eastern Cooperative Oncology Group	Phase 3	1993-04-01	RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission.
NCT00002517 ↗	Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 3	1993-03-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for acute myeloid leukemia or myelodysplastic syndrome. PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have newly diagnosed acute myeloid leukemia or myelodysplastic syndrome.
NCT00002531 ↗	Combination Chemotherapy in Treating Adults With Acute Lymphocytic Leukemia	Unknown status	Johann Wolfgang Goethe University Hospital	Phase 2	1993-01-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Randomized phase II trial to study the effectiveness of various combination chemotherapy regimens in treating patients with acute lymphocytic leukemia.

Clinical Trial Conditions for CYTARABINE; DAUNORUBICIN

Condition Name

Condition Name for CYTARABINE; DAUNORUBICIN
Intervention	Trials
Acute Myeloid Leukemia	94
Leukemia	81
Untreated Adult Acute Myeloid Leukemia	23
Acute Lymphoblastic Leukemia	19

Condition MeSH

Condition MeSH for CYTARABINE; DAUNORUBICIN
Intervention	Trials
Leukemia	254
Leukemia, Myeloid, Acute	192
Leukemia, Myeloid	164
Precursor Cell Lymphoblastic Leukemia-Lymphoma	84

Clinical Trial Locations for CYTARABINE; DAUNORUBICIN

Trials by Country

Trials by Country for CYTARABINE; DAUNORUBICIN
Location	Trials
Canada	231
Japan	54
China	40
Germany	39
Italy	37

Trials by US State

Trials by US State for CYTARABINE; DAUNORUBICIN
Location	Trials
New York	91
California	90
Illinois	86
Ohio	84
Texas	81

Clinical Trial Progress for CYTARABINE; DAUNORUBICIN

Clinical Trial Phase

Clinical Trial Phase for CYTARABINE; DAUNORUBICIN
Clinical Trial Phase	Trials
PHASE3	4
PHASE2	16
PHASE1	5

Clinical Trial Status

Clinical Trial Status for CYTARABINE; DAUNORUBICIN
Clinical Trial Phase	Trials
Completed	128
Recruiting	69
Active, not recruiting	31

Clinical Trial Sponsors for CYTARABINE; DAUNORUBICIN

Sponsor Name

Sponsor Name for CYTARABINE; DAUNORUBICIN
Sponsor	Trials
National Cancer Institute (NCI)	122
Children's Oncology Group	32
Jazz Pharmaceuticals	19

Sponsor Type

Sponsor Type for CYTARABINE; DAUNORUBICIN
Sponsor	Trials
Other	326
NIH	125
Industry	117

Cytarabine and Daunorubicin: Clinical Trial Landscape and Market Outlook

Last updated: February 19, 2026

This report analyzes the current clinical trial activity and projected market trends for cytarabine and daunorubicin, two established chemotherapy agents primarily used in the treatment of acute myeloid leukemia (AML). The analysis focuses on patent expiry, ongoing research, and competitive forces shaping their future.

What is the Current Clinical Trial Status for Cytarabine and Daunorubicin?

Both cytarabine and daunorubicin are older chemotherapeutic drugs with established roles in AML treatment. Their clinical trial landscape reflects efforts to:

• Improve formulations: Developing liposomal or other advanced delivery systems to enhance efficacy and reduce toxicity.
• Investigate new combinations: Exploring synergistic effects when used with newer targeted therapies or immunotherapies.
• Evaluate in different settings: Assessing their use in frontline therapy, relapsed/refractory disease, or in specific patient subgroups.
• Refine dosing and schedules: Optimizing treatment regimens to maximize therapeutic benefit and minimize adverse events.

Cytarabine Trials:

As of early 2024, clinical trials involving cytarabine are ongoing across various phases. Key areas of investigation include:

• Phase 3 Trials: Primarily focus on comparing novel combinations of cytarabine with other agents against standard-of-care chemotherapy or newer treatments for newly diagnosed or relapsed/refractory AML. Some trials aim to establish non-inferiority or superiority of cytarabine-based regimens in specific patient populations, such as older adults or those with poor-risk cytogenetics.
• Phase 2 Trials: Often explore the efficacy and safety of cytarabine in combination with emerging therapies, such as FLT3 inhibitors (e.g., gilteritinib), IDH inhibitors (e.g., ivosidenib, enasidenib), or BCL-2 inhibitors (e.g., venetoclax). These trials assess preliminary response rates, duration of response, and overall survival.
• Phase 1/2 Trials: Focus on dose-escalation and preliminary efficacy of novel cytarabine formulations, such as pegylated cytarabine, designed to prolong drug exposure and potentially improve therapeutic index.

Daunorubicin Trials:

Daunorubicin, often used in combination with cytarabine in the standard "7+3" induction regimen for AML, also sees continued clinical investigation:

• Phase 3 Trials: Similar to cytarabine, these trials often evaluate enhanced daunorubicin delivery systems or new combination regimens. For example, liposomal daunorubicin is being investigated in combination with cytarabine for improved outcomes in specific AML subtypes. Trials may also compare different anthracycline agents, including daunorubicin, in various treatment contexts.
• Phase 2 Trials: Research includes assessing daunorubicin in combination with targeted agents for patients with specific genetic mutations in AML. Investigations also look at reduced-intensity regimens or dose adjustments in elderly or frail patients.
• Phase 1 Trials: These trials may explore novel anthracycline analogs or fixed-dose combinations that include daunorubicin to assess safety and tolerability.

A significant portion of ongoing trials for both drugs are sponsored by academic institutions and governmental bodies, indicating a sustained interest in optimizing their use within established treatment paradigms. Pharmaceutical companies are also involved, particularly in trials exploring combinations with their proprietary novel agents or advanced formulations.

What is the Patent Landscape for Cytarabine and Daunorubicin?

The original patents for cytarabine and daunorubicin, developed decades ago, have long expired. This means that the active pharmaceutical ingredients themselves are off-patent and available as generics.

• Cytarabine: The compound was first synthesized in the 1950s, with key patents expiring by the mid-1970s to early 1980s.
• Daunorubicin: Discovered in the 1960s, its primary patents also expired by the late 1980s to early 1990s.

The patent landscape has shifted from the active drug substance to:

• Formulations: Patents may exist for specific formulations, such as liposomal preparations, sustained-release versions, or novel salt forms, designed to improve bioavailability, stability, or delivery characteristics. For example, liposomal daunorubicin has specific patent protection around its formulation technology.
• Manufacturing Processes: Novel or improved methods for synthesizing cytarabine or daunorubicin may be patentable if they offer significant advantages in terms of yield, purity, or cost-effectiveness.
• Combinations and Methods of Treatment: Patents can be obtained for specific drug combinations (e.g., cytarabine and venetoclax for AML) or for novel methods of administering these drugs for particular indications or patient populations. These patents are typically focused on the therapeutic use rather than the drug molecule itself.
• Polymorphs and Crystal Forms: New crystalline forms or polymorphs of cytarabine or daunorubicin, if demonstrating improved properties (e.g., solubility, stability), could be subject to patent protection.

The lack of primary patent protection for the drug molecules themselves significantly contributes to the availability of generic versions, driving down prices and increasing accessibility.

How is the Market for Cytarabine and Daunorubicin Evolving?

The market for cytarabine and daunorubicin is characterized by the dominance of generic products, but its evolution is shaped by the persistent need for effective AML treatments and the integration of these older agents with newer therapies.

Key Market Dynamics:

• Generic Dominance: Due to patent expiry, both drugs are widely available from multiple generic manufacturers. This has resulted in intense price competition and a market primarily driven by volume and cost-effectiveness.
• Continued Use in Standard of Care: The "7+3" regimen (cytarabine plus an anthracycline like daunorubicin) remains a cornerstone of induction therapy for newly diagnosed AML. This established efficacy ensures continued demand.
• Competition from Novel Agents: The rise of targeted therapies (e.g., FLT3 inhibitors, IDH inhibitors) and immunotherapies (e.g., bispecific antibodies) is altering the treatment landscape for AML. While these newer agents often target specific mutations or pathways, they are frequently used in combination with, or as alternatives to, conventional chemotherapy.
• Role in Combinations: The primary growth driver for cytarabine and daunorubicin in the near future is their incorporation into combination regimens with novel agents. Studies demonstrating improved outcomes when combining venetoclax with hypomethylating agents (like azacitidine or decitabine) or with cytarabine are increasing the use of these older drugs in novel contexts.
• Focus on Formulations and Delivery: Investments in developing advanced formulations, such as liposomal daunorubicin or investigational modified cytarabine, aim to improve the therapeutic index and potentially create niche markets for these proprietary versions. However, the cost-benefit analysis against generics remains a significant hurdle.
• Geographic Market Variations: Demand for generic cytarabine and daunorubicin is strong in both developed and emerging markets due to their affordability. Developed markets may see a greater adoption of novel combination therapies, while emerging markets will likely continue to rely heavily on cost-effective generic chemotherapy.

Market Projections:

The market for generic cytarabine and daunorubicin is projected to remain stable, supported by their established role in AML treatment. However, significant market expansion for the active pharmaceutical ingredients themselves is unlikely due to generic competition.

• Stable Demand for Generics: The fundamental need for cost-effective chemotherapy in AML will ensure a steady demand for generic cytarabine and daunorubicin. The global AML market size, while influenced by novel therapies, is substantial enough to maintain this demand.
• Growth in Combination Therapies: The market segment for specific formulations or branded combination therapies that include cytarabine or daunorubicin could see growth. For instance, branded combination therapies for relapsed/refractory AML or for specific genetic subtypes that incorporate these older drugs are likely to command premium pricing.
• Impact of New Entrants: The generic market is highly competitive, with multiple manufacturers. Profitability is often tied to manufacturing efficiency and supply chain management.
• Research & Development Investment: While the active drugs are off-patent, R&D continues on formulations and combinations. Success in clinical trials for novel combinations is the primary factor for potential market shifts.

The overall market trajectory suggests a sustained but largely mature market for the base generics, with potential for growth in specific, value-added formulations or combination products driven by clinical trial successes.

What are the Key Challenges and Opportunities?

Challenges:

• Toxicity: Both cytarabine and daunorubicin have significant toxicities, including myelosuppression, mucositis, and cardiotoxicity (for daunorubicin), which limit their use, especially in elderly or frail patients.
• Resistance Mechanisms: AML cells can develop resistance to these agents, reducing their long-term effectiveness.
• Competition from Novel Therapies: The development of targeted therapies and immunotherapies offers alternative or complementary treatment options that may displace older chemotherapy in certain patient populations.
• Pricing Pressure: The generic nature of these drugs leads to intense price competition, limiting profit margins for manufacturers.
• Complex Supply Chains: Ensuring a consistent and affordable global supply of these essential medicines requires robust manufacturing and distribution networks.

Opportunities:

• Combination Therapies: The most significant opportunity lies in developing and validating novel combination regimens that integrate cytarabine and daunorubicin with newer, targeted agents. This can enhance efficacy, overcome resistance, and potentially reduce toxicity compared to high-dose chemotherapy alone.
• Improved Formulations: Development of liposomal, pegylated, or other advanced formulations can improve drug delivery, prolong half-life, target specific tissues, and reduce off-target toxicity, potentially creating differentiated products.
• Personalized Medicine: Identifying patient subgroups that are more likely to benefit from cytarabine or daunorubicin-based regimens, based on genetic markers or other biomarkers, can lead to more precise and effective treatment strategies.
• Cost-Effectiveness in Emerging Markets: The affordability of generic cytarabine and daunorubicin makes them indispensable in healthcare systems with limited budgets, representing a stable and significant market.
• Repurposing and New Indications: While primarily used in AML, ongoing research may identify new therapeutic applications for these agents in other hematological malignancies or solid tumors.

Key Takeaways

• Cytarabine and daunorubicin are off-patent drugs with established roles in AML treatment, particularly in combination regimens like "7+3."
• Ongoing clinical trials focus on optimizing existing regimens through novel formulations and combinations with newer targeted and immunotherapies.
• The market is dominated by generic products, driving price competition and a focus on cost-effectiveness.
• The primary growth potential lies in value-added formulations and combination therapies that enhance efficacy or reduce toxicity.
• Challenges include drug toxicity, resistance, and competition from novel therapies, while opportunities exist in personalized medicine and cost-effective treatment strategies.

Frequently Asked Questions

1. Are there any new patents being filed for cytarabine or daunorubicin themselves? No new patents are being filed for the basic cytarabine or daunorubicin molecules as their original compound patents have long expired. Patent activity is focused on novel formulations, manufacturing processes, or specific therapeutic uses and combinations.

2. What is the market share of generic versus branded versions of cytarabine and daunorubicin? The market is overwhelmingly dominated by generic versions. Branded versions, if any, are typically linked to proprietary formulations or are historical remnants from the pre-generic era.

3. Which specific novel agents are most frequently being investigated in combination with cytarabine and daunorubicin? Key novel agents being investigated in combination include BCL-2 inhibitors (e.g., venetoclax), FLT3 inhibitors (e.g., gilteritinib, quizartinib), IDH inhibitors (e.g., ivosidenib, enasidenib), and various immunotherapies like bispecific antibodies.

4. What is the typical patent protection duration for a novel formulation of an existing drug like cytarabine? A patent for a novel formulation typically grants protection for 20 years from the filing date, subject to any patent term extensions that may be available based on regulatory review periods.

5. How do the clinical trial outcomes for new combination therapies impact the demand for generic cytarabine and daunorubicin? Positive clinical trial outcomes for new combination therapies that include cytarabine or daunorubicin can stabilize or increase demand for these generic agents, as they become integral components of improved treatment regimens. However, if novel therapies prove highly effective as standalone treatments, they could eventually reduce the reliance on older chemotherapy.

Cited Sources

[1] National Institutes of Health. (n.d.). ClinicalTrials.gov. Retrieved from https://clinicaltrials.gov/ [2] U.S. Food & Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-approved-drug-products-therapeutic-equivalence-evaluations [3] European Patent Office. (n.d.). Espacenet. Retrieved from https://www.epo.org/searching-services/espacenet.html [4] U.S. Patent and Trademark Office. (n.d.). Patent Public Search. Retrieved from https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html