CLINICAL TRIALS PROFILE FOR PENTOSTATIN

505(b)(2) Clinical Trials for pentostatin

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	NCT03249831 ↗	A Blood Stem Cell Transplant for Sickle Cell Disease	Recruiting	California Institute for Regenerative Medicine (CIRM)	Phase 1	2019-01-04	Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the immune system (which fight infections) and platelets (which help the blood clot). Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell transplant from a donor is a treatment option for patients with severe sickle cell disease. The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then make normal red blood cells - as well as other types of blood cells - in the patient. When blood cells from two people co-exist in the patient, this is called mixed chimerism. Most children are successfully treated with blood stem cells from a sibling (brother/sister) who completely shares their tissue type (full-matched donor). However, transplant is not an option for patients who (1) have serious medical problems, and/or (2) do not have a full-matched donor. Most patients will have a relative who shares half of their tissue type (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical donor). Adult patients with severe sickle cell disease were successfully treated with a half-matched transplant in a clinical study. Researchers would like to make half-matched transplant an option for more patients by (1) improving transplant success and (2) reducing transplanted-related complications. This research transplant is being tested in this Pilot study for the first time. It is different from a standard transplant because: 1. Half-matched related donors will be used, and 2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and 3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted) before giving the blood stem cell transplant to the patient to improve transplant outcomes. It is hoped that the research transplant: 1. Will reverse sickle cell disease and improve patient quality of life, 2. Will reduce side effects and help the patient recover faster from the transplant, 3. Help the patient keep the transplant longer and 4. Reduce serious transplant-related complications.
New Combination	NCT03249831 ↗	A Blood Stem Cell Transplant for Sickle Cell Disease	Recruiting	City of Hope Medical Center	Phase 1	2019-01-04	Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the immune system (which fight infections) and platelets (which help the blood clot). Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell transplant from a donor is a treatment option for patients with severe sickle cell disease. The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then make normal red blood cells - as well as other types of blood cells - in the patient. When blood cells from two people co-exist in the patient, this is called mixed chimerism. Most children are successfully treated with blood stem cells from a sibling (brother/sister) who completely shares their tissue type (full-matched donor). However, transplant is not an option for patients who (1) have serious medical problems, and/or (2) do not have a full-matched donor. Most patients will have a relative who shares half of their tissue type (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical donor). Adult patients with severe sickle cell disease were successfully treated with a half-matched transplant in a clinical study. Researchers would like to make half-matched transplant an option for more patients by (1) improving transplant success and (2) reducing transplanted-related complications. This research transplant is being tested in this Pilot study for the first time. It is different from a standard transplant because: 1. Half-matched related donors will be used, and 2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and 3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted) before giving the blood stem cell transplant to the patient to improve transplant outcomes. It is hoped that the research transplant: 1. Will reverse sickle cell disease and improve patient quality of life, 2. Will reduce side effects and help the patient recover faster from the transplant, 3. Help the patient keep the transplant longer and 4. Reduce serious transplant-related complications.

All Clinical Trials for pentostatin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00003005 ↗	Chemotherapy With Cordycepin Plus Pentostatin in Treating Patients With Refractory Acute Lymphocytic or Chronic Myelogenous Leukemia	Completed	National Cancer Institute (NCI)	Phase 1	1997-12-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of chemotherapy consisting of cordycepin plus pentostatin in treating patients with refractory acute lymphocytic or chronic myelogenous leukemia.
NCT00003005 ↗	Chemotherapy With Cordycepin Plus Pentostatin in Treating Patients With Refractory Acute Lymphocytic or Chronic Myelogenous Leukemia	Completed	Boston Medical Center	Phase 1	1997-12-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of chemotherapy consisting of cordycepin plus pentostatin in treating patients with refractory acute lymphocytic or chronic myelogenous leukemia.
NCT00003658 ↗	Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers	Completed	National Cancer Institute (NCI)	Phase 2	1998-09-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining pentostatin, cyclophosphamide, and rituximab in treating patients who have chronic lymphocytic leukemia or other B-cell cancers that have been treated previously.
NCT00003658 ↗	Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers	Completed	Memorial Sloan Kettering Cancer Center	Phase 2	1998-09-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining pentostatin, cyclophosphamide, and rituximab in treating patients who have chronic lymphocytic leukemia or other B-cell cancers that have been treated previously.
NCT00006968 ↗	Pentostatin Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Kidney Cancer	Completed	National Cancer Institute (NCI)	Phase 1/Phase 2	2000-09-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of pentostatin followed by peripheral stem cell transplantation in treating patients who have advanced kidney cancer.
NCT00006968 ↗	Pentostatin Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Kidney Cancer	Completed	Jonsson Comprehensive Cancer Center	Phase 1/Phase 2	2000-09-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of pentostatin followed by peripheral stem cell transplantation in treating patients who have advanced kidney cancer.

Clinical Trial Conditions for pentostatin

Condition Name

Condition Name for pentostatin
Intervention	Trials
Leukemia	18
Lymphoma	14
Chronic Lymphocytic Leukemia	7
Graft vs Host Disease	5

Condition MeSH

Condition MeSH for pentostatin
Intervention	Trials
Leukemia	29
Leukemia, Lymphoid	22
Leukemia, Lymphocytic, Chronic, B-Cell	21
Lymphoma	20

Clinical Trial Locations for pentostatin

Trials by Country

Trials by Country for pentostatin
Location	Trials
United States	217
Italy	19
Japan	10
Spain	9
Poland	3

Trials by US State

Trials by US State for pentostatin
Location	Trials
Maryland	22
Texas	15
New York	15
Minnesota	14
Florida	13

Clinical Trial Progress for pentostatin

Clinical Trial Phase

Clinical Trial Phase for pentostatin
Clinical Trial Phase	Trials
Phase 3	4
Phase 2	39
Phase 1/Phase 2	11

Clinical Trial Status

Clinical Trial Status for pentostatin
Clinical Trial Phase	Trials
Completed	35
Recruiting	9
Terminated	6

Clinical Trial Sponsors for pentostatin

Sponsor Name

Sponsor Name for pentostatin
Sponsor	Trials
National Cancer Institute (NCI)	30
Astex Pharmaceuticals	9
Astex Pharmaceuticals, Inc.	9

Sponsor Type

Sponsor Type for pentostatin
Sponsor	Trials
Other	55
Industry	37
NIH	37

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

Last updated: October 28, 2025

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Introduction

Pentostatin, a purine analog, operates as an adenosine deaminase (ADA) inhibitor, integral in treating certain hematologic malignancies, notably hairy cell leukemia (HCL), and other lymphoid cancers. First approved by the U.S. Food and Drug Administration (FDA) in 1991, pentostatin remains vital in oncology therapeutics. However, despite longstanding clinical use, recent innovations and pipeline developments could recalibrate its market dynamics. This report synthesizes recent clinical trial data, evaluates current market conditions, and projects future trends for pentostatin.

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Clinical Trials Update

Current Clinical Trials Landscape

Recent years have seen a decline in large-scale Phase III trials focusing solely on pentostatin. Nevertheless, ongoing studies aim to expand indications, refine dosing regimens, and explore combinatory strategies.

• Combination Therapy Trials: Several trials combine pentostatin with other agents like rituximab, bendamustine, or novel immunotherapies to improve efficacy and reduce resistance. For example, a phase II trial (NCT03529277) evaluates pentostatin with rituximab in relapsed or refractory HCL, revealing promising response rates exceeding 90% with manageable safety profiles.

• New Indications: Exploratory studies are investigating pentostatin's role in other lymphoid malignancies, such as chronic lymphocytic leukemia (CLL) and T-cell lymphomas, although these remain early-phase and preliminary.

• Immunomodulatory Potential: Research into pentostatin’s immunosuppressive applications, notably in graft-versus-host disease (GVHD), has produced mixed results. The phase I/II trial (NCT02883257) exploring pentostatin for GVHD prophylaxis noted safety but limited efficacy, constraining further development in this space.

Safety and Efficacy Data

Historical data confirm pentostatin's efficacy in inducing remission in hairy cell leukemia, with long-term follow-up indicating durable responses. Newer trials reinforce its tolerability and manageable side effect profile, especially relative to other chemotherapies. Notably:

• Hematologic toxicities such as neutropenia and thrombocytopenia continue to be the principal adverse effects.

• Efforts to optimize dosing, reducing cumulative toxicity without compromising efficacy, are ongoing.

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Market Analysis

Current Market Dynamics

The pentostatin market remains relatively niche, primarily serving hematologic oncology indications. Estimated global sales from established markets (the US, EU, and parts of Asia) ranged between $50 million and $80 million annually over the past five years, according to IQVIA data. The primary driver remains the treatment of hairy cell leukemia, where pentostatin was historically a second-line agent prior to the advent of targeted therapies.

Competitive Landscape

• Established competitors include cladribine (2-CdA), another purine analog with broader indications. Cladribine has gained prominence due to its convenient dosing schedule and robust efficacy data, gradually overshadowing pentostatin in certain markets.

• Emerging agents: Targeted therapies such as BTK inhibitors (e.g., ibrutinib) and Bcl-2 inhibitors (venetoclax) are increasingly replacing traditional chemotherapeutics for lymphoid malignancies. These agents offer oral administration, improved tolerability, and effective disease control.

• Generic Status: Pentostatin's patent expired decades ago, leading to generic formulations that suppress pricing and limit profit margins. This reduces incentive for pharmaceutical companies to invest heavily in marketing or pipeline expansion.

Market Drivers and Barriers

• Drivers:

  • Long-standing clinical efficacy in hairy cell leukemia.
  • Low-cost generic formulations.
  • Continued use in select refractory cases.

• Barriers:

  • Competition from newer, targeted agents with better safety profiles.
  • Declining treatment shares owing to emerging therapies; for instance, BTK inhibitors have seen substantial approval for CLL and Waldenström macroglobulinemia.
  • Limited pipeline activity discourages new market entrants.

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Future Market Projections

Market Trends and Outlook (2023-2033)

• Declining Market Share: The overall market for pentostatin is projected to shrink steadily over the next decade, driven by the rising adoption of targeted therapies and monoclonal antibody combinations.

• Niche Applications: Pentostatin is likely to consolidate its role in highly refractory hairy cell leukemia cases, especially where newer agents are contraindicated or ineffective, preserving a small but stable market segment.

• Potential Revitalization:

  • Combination Regimens: Promising phase II data suggest that pentostatin combined with immunotherapies might resuscitate interest.
  • Biomarker-Driven Therapy: Advances in molecular diagnostics could identify patient subpopulations with a predisposition for pentostatin responsiveness, expanding its utilization.

• Geographic Variations:

  • In regions with limited access to high-cost targeted agents, pentostatin remains relevant and may see stable or slightly increased demand.
  • Conversely, in advanced healthcare markets, its use diminishes further.

Strategic Implications

Pharmaceutical companies may view pentostatin as a legacy drug. Investment in pipeline expansion appears limited, but opportunities exist in niche markets, particularly if new combination protocols demonstrate significant clinical benefit. Partnering with academic institutions to explore innovative indications could sustain relevance.

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Key Takeaways

• Pentostatin's clinical relevance persists in refractory hairy cell leukemia; however, the advent of targeted therapies diminishes its broader oncology footprint.
• Ongoing trials mainly focus on combination approaches and expanding indications, but these are predominantly early-stage and lack significant momentum.
• Market projections indicate continued decline in sales, with opportunities mainly confined to niche applications where newer treatments are unsuitable or unavailable.
• The generic status of pentostatin constrains profitability, discouraging substantial R&D investments.
• Strategic considerations should emphasize specialized use, exploring synergistic combination regimens, and leveraging molecular diagnostics to identify suitable patient subpopulations.

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FAQs

1. Is pentostatin still a frontline treatment for hairy cell leukemia?
No. While historically used as a primary therapy, pentostatin has largely been supplanted by cladribine and newer targeted agents, which offer similar or superior efficacy with more convenient dosing and safety profiles.

2. Are there any promising new indications for pentostatin?
Currently, research is preliminary. Some trials are examining its use in other lymphoid cancers and immunosuppressive conditions, but none have reached advanced clinical approval stages.

3. What are the main safety concerns associated with pentostatin?
Neutropenia, thrombocytopenia, and increased infection risk are primary. Long-term toxicity is manageable but warrants monitoring and dose adjustments.

4. How does pentostatin compare to newer therapies in terms of cost?
Generic pentostatin is significantly cheaper than newer targeted therapies; however, the reduced efficacy and safety advantages of newer agents influence overall treatment value.

5. Will pentostatin regain market share in the future?
Unlikely in primary indications due to competition from targeted agents. Its niche role may persist if combination strategies or biomarkers expand its utility.

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References

[1] FDA. Pentostatin (Nipent) Prescribing Information. 1991.
[2] IQVIA. Global Oncology Market Analysis Reports. 2022.
[3] US National Library of Medicine. ClinicalTrials.gov. Database entries for pentostatin. Various.