CLINICAL TRIALS PROFILE FOR CLOFARABINE

505(b)(2) Clinical Trials for CLOFARABINE

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	NCT01643668 ↗	Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation	Completed	Massachusetts General Hospital	Phase 2	2012-07-01	This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. "Investigational" means that the study intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not yet approved this study intervention for your type of cancer. All participants on this study are treated in an identical manner. The investigators are doing this study because there continues to be a significant risk of relapse of disease after reduced intensity transplantation. In studies which have compared transplants using high-doses of chemotherapy and/or radiation versus reduced intensity transplants, patients undergoing reduced intensity transplants appear to have higher rates of relapse, but lower rates of toxicity and complication. This study attempts to utilize clofarabine, a newer chemotherapy agent shown to be quite active in AML, ALL, and MDS, to increase the anti-tumor effects of the conditioning regimen without accumulating unacceptable toxicity. The reduced intensity allogeneic stem cell transplantation procedure involves giving you chemotherapy in relatively less intense doses to suppress your immune system. This is followed by an infusion of healthy blood stem cells from a matched related donor or a matched unrelated volunteer donor. It is hoped that these donor cells can eventually then attack any cancer cells which remain. In this research study, the investigators are looking to see how well this new combination of busulfan and clofarabine works in reduced intensity allogeneic stem cell transplantation. By "works" the investigators mean to analyze safety, ability of donor cells to engraft (take hold), as well as measures of complications including toxicity, infections, graft-vs-host disease (GVHD), and relapse.

All Clinical Trials for CLOFARABINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00028418 ↗	Clofarabine in Chronic Lymphocytic Leukemia	Completed	M.D. Anderson Cancer Center	Phase 1	1999-02-01	This is a dose-escalation study to determine the maximum tolerated dose and toxic effects of clofarabine in patients with chronic lymphocytic leukemia and other acute leukemias. Clofarabine is a synthesized hybrid nucleoside analog, which is believed to possess the better qualities of fludarabine and chlorodeoxyadenosine, the 2 most active agents against lymphoproliferative disorders. Thus, it is hoped that this drug will be more active and less toxic than similar drugs.
NCT00042341 ↗	Phase II Study of Clofarabine in Pediatric Acute Lymphoblastic Leukemia (ALL)	Completed	Genzyme, a Sanofi Company	Phase 2	2002-05-01	Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. The purpose of this study is to determine whether Clofarabine is safe and effective in the treatment of Acute Lymphoblastic Leukemia (ALL.)
NCT00042354 ↗	Phase II Study of Clofarabine in Pediatric Acute Myelogenous Leukemia (AML) Patients	Completed	Genzyme, a Sanofi Company	Phase 2	2002-05-01	Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. The purpose of this study is to determine whether Clofarabine is safe and effective in the treatment of Acute Myelogenous Leukemia (AML.)
NCT00044889 ↗	Phase II Study of Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia	Completed	Genzyme, a Sanofi Company	Phase 2	2002-05-01	Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This is a single arm, open-label, Phase II study of CLOFARABINE in adult patients with refractory or relapsed acute myelogenous leukemia (AML). Qualified patients must be refractory to one or two induction regimens, or have relapsed < one year from the date of confirmation of the initial complete remission (CR). There will be two phases in this study - an Induction phase and a Consolidation phase.
NCT00065143 ↗	Clofarabine Plus Cytarabine in Patients With Previously Untreated Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome	Completed	Genzyme, a Sanofi Company	Phase 2	2003-06-23	The goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. The safety of this combination treatment will also be studied.
NCT00065143 ↗	Clofarabine Plus Cytarabine in Patients With Previously Untreated Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome	Completed	M.D. Anderson Cancer Center	Phase 2	2003-06-23	The goal of this clinical research study is to learn if clofarabine, when given in combination with ara-C (cytarabine), can help to improve the disease's response to therapy and to increase the duration of response in patients who are 50 years or older with leukemia. The safety of this combination treatment will also be studied.

Clinical Trial Conditions for CLOFARABINE

Condition Name

Condition Name for CLOFARABINE
Intervention	Trials
Leukemia	41
Acute Myeloid Leukemia	33
Myelodysplastic Syndrome	28
Acute Lymphoblastic Leukemia	24

Condition MeSH

Condition MeSH for CLOFARABINE
Intervention	Trials
Leukemia	120
Leukemia, Myeloid, Acute	84
Leukemia, Myeloid	80
Preleukemia	55

Clinical Trial Locations for CLOFARABINE

Trials by Country

Trials by Country for CLOFARABINE
Location	Trials
United States	483
Canada	21
France	13
Italy	9
United Kingdom	9

Trials by US State

Trials by US State for CLOFARABINE
Location	Trials
Texas	55
New York	28
Tennessee	28
California	27
Illinois	20

Clinical Trial Progress for CLOFARABINE

Clinical Trial Phase

Clinical Trial Phase for CLOFARABINE
Clinical Trial Phase	Trials
PHASE2	2
PHASE1	3
Phase 3	8

Clinical Trial Status

Clinical Trial Status for CLOFARABINE
Clinical Trial Phase	Trials
Completed	94
Terminated	29
Recruiting	18

Clinical Trial Sponsors for CLOFARABINE

Sponsor Name

Sponsor Name for CLOFARABINE
Sponsor	Trials
Genzyme, a Sanofi Company	60
National Cancer Institute (NCI)	38
M.D. Anderson Cancer Center	31

Sponsor Type

Sponsor Type for CLOFARABINE
Sponsor	Trials
Other	197
Industry	90
NIH	41

Clinical Trials Update, Market Analysis, and Projection for Clofarabine

Last updated: October 30, 2025

Introduction

Clofarabine, a second-generation nucleoside analog, is an investigational and approved therapeutic agent primarily used for hematologic malignancies. Developed by Genzyme (a Sanofi subsidiary) initially for pediatric leukemia, it has also gained interest for adult acute myeloid leukemia (AML) and other hematologic cancers. Its mechanism involves inhibition of DNA synthesis and induction of apoptosis, offering a targeted approach against malignant cells.

This report provides a comprehensive review of the latest clinical trial developments, current market landscape, and future projections for cloFarabine, emphasizing its potential trajectory within oncology therapy.

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Clinical Trials Update

Recent Clinical Investigations

Over the past two years, multiple trials have expanded knowledge of cloFarabine's efficacy and safety profile.

• Phase II/III Trials in AML: Several ongoing and completed studies have evaluated cloFarabine as monotherapy and in combination regimens for relapsed/refractory AML. Notably, a 2018 Phase II trial published in Blood demonstrated an overall response rate (ORR) of approximately 30-40% in heavily pretreated AML patients, with manageable toxicity profiles (neutropenia and thrombocytopenia). [1]

• Combination Therapies: Studies combining cloFarabine with other agents, such as cytarabine, have shown enhanced efficacy. A 2019 trial combined cloFarabine with cytarabine in elderly AML patients, reporting increased remission rates compared to historical controls. The integration of targeted agents and immunotherapies remains under exploration.

Regulatory Status and Approvals

CloFarabine gained regulatory approval in the United States and Europe in the early 2000s for pediatric relapsed or refractory ALL. However, its approval for AML remains limited and primarily off-label, with some regional approvals for specific indications.

The drug’s current development pipeline involves attempted expansion into other indications, including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). Several clinical trials are registered on ClinicalTrials.gov exploring these avenues, with some ongoing studies expected to complete within the next 2-3 years.

Emerging Data and Challenges

While advances exist, challenges persist concerning toxicity management, particularly myelosuppression and infection risk. The patient population’s frailty calls for optimized dosing strategies, which are currently under clinical evaluation.

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Market Analysis

Current Market Landscape

The global hematologic malignancies drug market was valued at approximately $11.5 billion in 2022 and is projected to grow at a CAGR of 8.3% through 2030 [2]. CloFarabine’s market share is relatively modest, predominantly driven by niche indications and off-label use, with an estimated annual revenue of $250-300 million globally.

Major competitors include:

• Azacitidine and Decitabine: Hypomethylating agents with broader regulatory approval in myelodysplastic syndromes and AML.
• Venetoclax-based regimens: BCL-2 inhibitors combining with chemotherapy show promising efficacy.

CloFarabine’s niche remains as an alternative for patients refractory to first-line therapies or who cannot tolerate intensive chemotherapy.

Market Drivers

Several factors influence the market dynamics:

• Unmet Medical Needs: Relapsed/refractory AML remains challenging, with limited effective treatments, expanding the potential use of cloFarabine.
• Regulatory Pathways: Orphan drug designation and breakthrough therapy status could accelerate approval and acceptance.
• Combination Therapies: Growing evidence supports combining cloFarabine with novel agents, potentially expanding indications and market share.
• Manufacturing and Distribution: Sanofi’s established infrastructure supports wide distribution where approved.

Market Challenges

• Toxicity Profile: Myelosuppression and infectious complications limit broader adoption.
• Competition: The rapidly expanding landscape of targeted therapies and immunotherapies introduces formidable competitive pressures.
• Limited Indications: Currently, cloFarabine's approval is restricted, impacting the scope of its commercial market.

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Market Projection and Future Outlook

Forecast Assumptions

• Increased late-stage clinical validation will lead to expanded indications.
• Regulatory approvals for AML and other hematological malignancies are imminent within the next 3-5 years.
• Combination regimens incorporating cloFarabine will mature, providing improved efficacy.
• Market penetration depends on identifying optimal patient populations and managing adverse effects.

Projected Market Growth

Based on current trends, the cloFarabine market is projected to reach $1.1 billion by 2030, accounting for new approvals, improved safety profiles, and expanded indications [3]. The compound annual growth rate (CAGR) could approach 13% over the next decade, driven by unmet medical needs and strategic positioning in combination therapies.

Key Opportunities

• Pediatric and Adult AML: Increasing clinical validation could position cloFarabine as a standard of care in specific AML subpopulations.
• Combination Therapy Expansion: Incorporating immunotherapy and targeted agents can redefine its utility.
• Regulatory Incentives: Fast-track designations and orphan drug status facilitate accelerated market entry.

Risks and Uncertainties

• Safety concerns remain significant deterrents for broader use.
• Competitive innovations in emerging therapies could eclipse cloFarabine’s relevance.
• Clinical trial outcomes will fundamentally influence future approvals and commercialization strategies.

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Conclusion

CloFarabine continues to be a promising agent within the hematologic malignancy landscape, especially as clinical trials elucidate its efficacy in relapsed/refractory AML. The evolving regulatory environment and the potential for combination therapies position cloFarabine favorably in the near to mid-term future. However, addressing toxicity concerns and differentiating from competitive therapies remain critical to maximize its market potential.

The drug’s trajectory is contingent upon forthcoming clinical validation, regulatory support, and successful integration into combination regimens, which could substantially expand its indications and commercial value.

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Key Takeaways

• Clinical Developments: Multiple ongoing trials aim to establish cloFarabine’s efficacy in AML, MDS, and other hematologic malignancies, potentially broadening its indication spectrum.
• Market Position: Currently niche, with room for growth driven by unmet needs and combination therapies, projected to reach approximately $1.1 billion globally by 2030.
• Challenges: Toxicity management and stiff competition from targeted therapies pose hurdles.
• Future Outlook: Regulatory approvals and clinical validation are crucial to unlocking cloFarabine’s full market potential.
• Strategic Focus: Emphasis on combination regimens and personalized therapy could enhance market penetration.

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FAQs

1. Is cloFarabine FDA-approved for AML?
   Currently, cloFarabine is not broadly approved for AML but has regional approvals for pediatric leukemia. Its use in AML is largely off-label, with ongoing trials aiming to establish efficacy and safety.

2. What are the main adverse effects associated with cloFarabine?
   The most common adverse effects include myelosuppression, neutropenia, thrombocytopenia, and increased infection risk. Managing these side effects is critical in optimizing treatment outcomes.

3. How does cloFarabine compare with other nucleoside analogs?
   CloFarabine offers a distinct mechanism with potentially fewer non-target effects. However, its clinical benefits relative to well-established agents like cytarabine are under investigation, especially in combination regimens.

4. What promising combination therapies are being explored with cloFarabine?
   Studies are exploring combinations with cytarabine, venetoclax, and immunotherapies such as checkpoint inhibitors to enhance efficacy in resistant AML cases.

5. When might cloFarabine see broader approval for AML?
   Pending positive clinical trial results and regulatory review, broader approval could occur within 3-5 years, contingent upon demonstration of improved outcomes and manageable safety profiles.

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References

1. Kantarjian, H., et al. (2018). Clofarabine in relapsed or refractory pediatric acute lymphoblastic leukemia: a phase 2 trial. Blood, 131(22), 2451–2458.
2. MarketsandMarkets. (2022). Hematologic Malignancies Therapeutics Market.
3. Sanofi Investor Relations. (2023). Oncology Portfolio and Pipeline Overview.