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

• Status: Terminated
• Trial end date: 2018-05-10
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: GlaxoSmithKline; Novartis
• Treatments: Antibodies, Monoclonal; Bendamustine Hydrochloride; Ofatumumab; Pentostatin

Criteria

Inclusion Criteria:

1. 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.

2. 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.

3. Age ≥ 18 years of age.

4. ECOG performance statue 0 to 2.

5. Reasonable life-expectancy greater than 12 weeks.

6. Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment.

7. Signed informed consent, which indicates the investigational nature of this study, is required.

8. No patient may be entered onto the study without consultation with the principal investigator or his designee.

Exclusion Criteria:

1. 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)

2. No prior cytotoxic therapy for at least 4 weeks before enrollment.

3. Currently participating in any other interventional clinical study.

4. Other currently active malignancy.

5. Active uncontrolled infection.

6. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.

7. Known HIV positive.

8. 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.

9. 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.

10. 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.

11. 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

12. Screening laboratory values:

1. 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.

2. total bilirubin > 2 times upper normal limit (unless due to tumor involvement of liver or a known history of Gilbert's disease)

3. ALT (alanine transaminase) > 2.5 times upper normal limit (unless due to disease involvement of liver.

13. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.

14. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.

15. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy