NCT01059786

Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia

Active, enrolled Phase 2 Results posted Last updated 12 June 2025

What this trial tests

Phase 2 trial testing Pentostatin in Hairy Cell Leukemia in 69 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 July 2010

Primary endpoint
15 December 2022

31 December 2027

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	69
Start date	1 July 2010
Primary completion	15 December 2022
Estimated completion	31 December 2027
Sites	1 location across United States

Drugs / interventions tested

• Pentostatin (PENTOSTATIN) — full drug profile →
• Rituximab
• Bendamustine (BENDAMUSTINE) — full drug profile →
• Acetaminophen
• Diphenhydramine (diphenhydramine) — full drug profile →
• Epinephrine (epinephrine) — full drug profile →
• Antihistamines
• Corticosteroids
• Bronchodilators — full drug profile →
• Intravenous (IV) Saline

Conditions studied

• Hairy Cell Leukemia — all drugs for Hairy Cell Leukemia →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Hairy Cell Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Receiving Pentostatin + Rituximab and Bendamustine + Rituximab Who Achieve a Complete Remission (CR) + Partial Response (PR) Primary · At end of treatment, approximately 6 months

Number of participants receiving pentostatin + rituximab and bendamustine + rituximab who achieve a CR +PR measured by the following response criteria. Complete remission is all of the following for at least 4 weeks: absolute neutrophil count ≥ 1500/mm\^3, platelets ≥ 100,000/mm\^3, hemoglobin ≥ 11g/dl, spleen non-palpable below the costal margin, or not below costal margin on computed tomography, and circulating hairy cell leukemia (HCL) cells either non-visible on Wright stain or \< 1% by flow cytometry. Partial response is all of the following for at least 4 weeks: neutrophils ≥ 1,500/µL or

Complete Remission

Group	Value	95% CI
Non-Randomized to 70 mg/m2 Bendamustine-Rituximab	3
Non-randomized to 90 mg/m^2 Bendamustine-Rituximab	4
Randomized to 90 mg/m^2 Bendamustine-Rituximab	20
Randomized to Pentostatin-Rituximab	22
Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab	1

Partial Response

Group	Value	95% CI
Non-Randomized to 70 mg/m2 Bendamustine-Rituximab	3
Non-randomized to 90 mg/m^2 Bendamustine-Rituximab	2
Randomized to 90 mg/m^2 Bendamustine-Rituximab	4
Randomized to Pentostatin-Rituximab	4
Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab	0

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) Secondary · Date treatment consent signed to date off study, approximately 103 months and 19 days; 133 months and 11 days; 111 months and 15 days; 102 months and 25 days; 44 months and 14 days; and 19 months and 2 days for each group respectively.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

Group	Value	95% CI
Non-Randomized to 70 mg/m2 Bendamustine-Rituximab	6
Non-randomized to 90 mg/m^2 Bendamustine-Rituximab	6
Randomized to 90 mg/m^2 Bendamustine-Rituximab	28
Randomized to Pentostatin-Rituximab	28
Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 103 months and 19 days; 133 months and 11 days; 111 months and 15 days; 102 months and 25 days; 44 months and 14 days; and 19 months and 2 days for each group respectively.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Non-Randomized to 70 mg/m2 Bendamustine-Rituximab

Serious: 0/6 (0%)

Deaths: 0/6

Non-randomized to 90 mg/m^2 Bendamustine-Rituximab

Serious: 0/6 (0%)

Deaths: 0/6

Randomized to 90 mg/m^2 Bendamustine-Rituximab

Serious: 8/28 (29%)

Deaths: 3/28

Randomized to Pentostatin-Rituximab

Serious: 7/28 (25%)

Deaths: 5/28

Non-randomized to Bendamustine 90mg/m^2 or Pentostatin 4mg/m^2 With Rituximab

Serious: 0/1 (0%)

Deaths: 0/1

Serious adverse events (21 terms)

Reaction	System	Non-Randomized to 70 mg/m2…	Non-randomized to 90 mg/m^…	Randomized to 90 mg/m^2 Be…	Randomized to Pentostatin-…	Non-randomized to Bendamus…
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Allergic reaction	Immune system disorders	—	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—
Upper respiratory infection	Infections and infestations	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—
Chills	General disorders	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—
Edema face	General disorders	—	—	—	—	—
Enterocolitis infectious	Infections and infestations	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—	—	—
Tumor lysis syndrome	Metabolism and nutrition disorders	—	—	—	—	—
Vasovagal reaction	Nervous system disorders	—	—	—	—	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—

Other adverse events (166 terms — click to expand)

Reaction	System	Non-Randomized to 70 mg/m2…	Non-randomized to 90 mg/m^…	Randomized to 90 mg/m^2 Be…	Randomized to Pentostatin-…	Non-randomized to Bendamus…
Lymphocyte count decreased	Investigations	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—	—
Chills	General disorders	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Fever	General disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Non-cardiac chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—	—	—
Allergic reaction	Immune system disorders	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Creatinine increased	Investigations	—	—	—	—	—
Edema limbs	General disorders	—	—	—	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—
CD4 lymphocytes decreased	Investigations	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Infusion related reaction	General disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—

Most-reported serious reactions: Febrile neutropenia, Allergic reaction, Dyspnea, Lung infection, Syncope, Upper respiratory infection, Acute kidney injury, Chills.

Data from ClinicalTrials.gov NCT01059786 adverse events section.

Sponsor's own description

Background:

* Researchers are attempting to develop new treatments for hairy cell leukemia (HCL) that has not responded well to or has recurred after standard HCL therapies. One nonstandard treatment for HCL is rituximab, an antibody that binds to the cancer cells and helps the immune system destroy them. By combining rituximab with other anti-cancer drugs, researchers hope to determine whether the combined drugs are successful in treating HCL.
* Pentostatin and bendamustine are two anti-cancer drugs that have been used to treat different kinds of blood and immune system cancers. Bendamustine is approved to treat other kinds of leukemia and lymphoma, but it has not been used to treat HCL. Pentostatin has been used for more than 20 years to treat HCL, but it has not been combined with rituximab in official clinical trials.

Objectives:

* To determine whether rituximab with either pentostatin or bendamustine is a more effective treatment for HCL than rituximab alone.
* To determine whether pentostatin or bendamustine is a more effective treatment for HCL when combined with rituximab.

Eligibility:

\- Individuals at least 18 years of age who have been diagnosed with hairy cell leukemia that has not responded well to or has relapsed after standard HCL therapies.

Design:

* The study will last for four treatment cycles of 28 days each.
* Prior to the study, participants will be screened with a full medical history and physical exam, bone marrow biopsy (if one has not been performed in the last 6 months), computed tomography (CT) or ultrasound scan, tumor measurements, and other tests as required by the researchers. Participants will provide blood and urine samples at this time as well.
* Rituximab with bendamustine: Participants will receive rituximab on Days 1 and 15 of each cycle and bendamustine on Days 1 and 2 of each cycle, for a total of four cycles.
* Rituximab with pentostatin: Participants will receive rituximab on Days 1 and 15 of each cycle and pentostatin on rituximab on Days 1 and 15 of each cycle, for a total of four cycles.
* Participants will have regular tests during the treatment cycles, including bone marrow biopsies and CT or ultrasound scans. Participants will also provide regular blood and urine samples to assess the results of treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Adenosine Metabolism: Emerging Concepts for Cancer Therapy.
   Boison D, Yegutkin GG. · · 2019 · cited 251× · PMID 31821783 · DOI 10.1016/j.ccell.2019.10.007
2. The hypoxia-adenosine link during inflammation.
   Bowser JL, Lee JW, Yuan X, Eltzschig HK. · · 2017 · cited 90× · PMID 28798196 · DOI 10.1152/japplphysiol.00101.2017
3. Bendamustine and rituximab in relapsed and refractory hairy cell leukemia.
   Burotto M, Stetler-Stevenson M, Arons E, Zhou H, et al · · 2013 · cited 55× · PMID 24097860 · DOI 10.1158/1078-0432.ccr-13-1848
4. Differential Expression of CD43, CD81, and CD200 in Classic Versus Variant Hairy Cell Leukemia.
   Salem DA, Scott D, McCoy CS, Liewehr DJ, et al · · 2019 · cited 19× · PMID 31077558 · DOI 10.1002/cyto.b.21785
5. Treatment of Classic Hairy Cell Leukemia: Targeting Minimal Residual Disease beyond Cladribine.
   Bohn JP, Dietrich S. · · 2022 · cited 8× · PMID 35205704 · DOI 10.3390/cancers14040956
6. Concurrent chronic lymphocytic leukemia/small lymphocytic lymphoma and hairy cell leukemia: clinical, pathologic and molecular features.
   Obiorah IE, Francischetti IMB, Wang HW, Ahn IE, et al · · 2020 · cited 6× · PMID 32755330 · DOI 10.1080/10428194.2020.1797007
7. Current and emerging treatment options for hairy cell leukemia.
   López-Rubio M, Garcia-Marco JA. · · 2015 · cited 4× · PMID 26316784 · DOI 10.2147/ott.s70316
8. The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.
   Gargiulo E, Giordano M, Niemann CU, Moussay E, et al · · 2023 · cited 2× · PMID 36968995 · DOI 10.3389/fonc.2023.1122699