Combination of Pentostatin, Bendamustine and Ofatumumab for Treatment of Chronic Lymphocytic Leukemia and Lymphoma

NCT01352312 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: 11P.1662011-23OFT114197JT 1680
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study with Cohort Expansion of Pentostatin, Bendamustine and Ofatumumab (PBO) for patients with previously treated Chronic Lymphocytic Leukemia (CLL) and B-cell Non-Hodgkin's Lymphoma (B- cell NHL). The purpose of this study is to determine the optimal dose of bendamustine in combination with pentostatin and ofatumumab, and then to see how safe these three drugs work together.

Conditions

Chronic Lymphocytic Leukemia; B-Cell Non-Hodgkin's Lymphoma

Keywords

Chronic Lymphocytic Leukemia; Non-Hodgkin's Lymphoma; B-cell; leukemia; lymphoma; bendamustine; pentostatin; ofatumumab; NHL; CLL

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Bendamustine

  The primary objective of this study is to determine the dose of bendamustine in combination with pentostatin and ofatumumab at which \<33% of patients with relapsed Non-Hodgkin's Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) experience severe toxicity; and to assess the toxicity of this regimen.

  Up to 6 months

• Dose Limiting Toxicity (DLT)

  Dose limiting toxicity (DLT) will be defined as any grade 4 infection, or grade ≥ 3 non-hematologic toxicity that persists for 7 days or more. Safety Issue?: (FDAAA) Yes

  Through one year post-treatment

Secondary Outcomes (1)

• Efficacy of Study Treatment Regimen

  3 and 6 months

Study Arms (1)

Treatment (pentostatin, bendamustine, ofatumumab)

EXPERIMENTAL

Patients receive bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2, pentostatin IV on day 1, and ofatumumab IV on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bendamustine; Drug: Pentostatin; Drug: Ofatumumab

Interventions

Bendamustine DRUG

Bendamustine at the dose of 50 mg/m2 (or 70 or 90 or 40 mg/m2 depending on the dose level) daily on day 1 and 2.

Also known as: Ribomustin, Treanda, SDX-105

Treatment (pentostatin, bendamustine, ofatumumab)

Pentostatin DRUG

Pentostatin 4 mg/m2 on day 1 of each cycle. For patients with estimated or measured glomerular filtration rate (GFR) 30 to 60 ml/min/m2 pentostatin will be administered at the reduced dose of 2 mg/m2 on day 1 of each cycle.

Also known as: deoxycoformycin

Treatment (pentostatin, bendamustine, ofatumumab)

Ofatumumab DRUG

Ofatumumab 300 mg on day 2 of first cycle. Subsequently, from cycle 2 to 6, ofatumumab 1000 mg on day 2 will be administered.

Also known as: Arzerra, HuMax-CD20

Treatment (pentostatin, bendamustine, ofatumumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously treated CLL or other B-cell neoplasm including small lymphocytic lymphoma, hairy cell leukemia, follicular, lymphoma, Waldenstrom's macroglobulinemia, marginal zone lymphomas, mantle cell lymphomas, lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma. Patients with composite lymphoma and transformed disease will be included. Immunophenotypic (or immunohistochemical) analysis of the malignant lymphocytes should demonstrate that the cells are B-cells.
• Patients must have had prior cytotoxic therapy for their disease. Patients with diffuse large B-cell lymphoma must have been treated with at least 2 prior cytotoxic therapies.
• Age ≥ 18 years of age.
• ECOG performance statue 0 to 2.
• Reasonable life-expectancy greater than 12 weeks.
• Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment.
• Signed informed consent, which indicates the investigational nature of this study, is required.
• No patient may be entered onto the study without consultation with the principal investigator or his designee.

You may not qualify if:

• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• No prior cytotoxic therapy for at least 4 weeks before enrollment.
• Currently participating in any other interventional clinical study.
• Other currently active malignancy.
• Active uncontrolled infection.
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
• Known HIV positive.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and uncontrolled symptomatic arrhythmia.
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
• Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
• Active hepatitis C infection. If positive serology for hepatitis C (HC) defined as a positive test for HCAb, HC quantitative PCR will be performed. If PCR is positive the subject will be excluded
• Screening laboratory values:
• creatinine \> 2.0 times upper normal limit and creatinine clearance \< 30 ml/min/m2. Patients with creatinine \> 2 times upper limit of normal will have creatinine clearance estimated. At the discretion of treating physician, creatinine clearance can be measured and that value can be used instead of calculated creatinine clearance.
• total bilirubin \> 2 times upper normal limit (unless due to tumor involvement of liver or a known history of Gilbert's disease)
• ALT (alanine transaminase) \> 2.5 times upper normal limit (unless due to disease involvement of liver.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Leukemia; Lymphoma

Interventions

Bendamustine Hydrochloride; Pentostatin; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jo Fili, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2011
• First Posted: May 11, 2011
• Study Start: May 25, 2011
• Primary Completion: April 8, 2016
• Study Completion: May 10, 2018
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (1)