Combination of Pentostatin, Bendamustine and Ofatumumab for Treatment of Chronic Lymphocytic Leukemia and Lymphoma
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.
Chronic Lymphocytic Leukemia
B-Cell Non-Hodgkin's Lymphoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial With Cohort Expansion of Pentostatin, Bendamustine and Ofatumumab (PBO) for the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma|
- Maximum Tolerated Dose (MTD) of Bendamustine [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]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.
- Dose Limiting Toxicity (DLT) [ Time Frame: Through one year post-treatment ] [ Designated as safety issue: Yes ]
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
- Efficacy of Study Treatment Regimen [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
- CBC (complete blood count)
- B-cell count
- If a patient is in CR (complete recovery) by other criteria then bone marrow aspiration/biopsy will be performed.
- CT (x-ray computed tomography) scan of chest/abdomen/pelvis (optional in patients with CLL)
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pentostatin, bendamustine, ofatumumab)
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.
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.
Other Names:Drug: Pentostatin
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.
Other Name: deoxycoformycinDrug: Ofatumumab
Ofatumumab 300 mg on day 2 of first cycle. Subsequently, from cycle 2 to 6, ofatumumab 1000 mg on day 2 will be administered.
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. There has been considerable progress in understanding the biology and treatment of CLL in the last 20 years. However, even with modern therapies, complete responses (CR) are achieved in approximately 25% of the patients with relapsed/refractory disease. Multiple studies have demonstrated that patients who achieve CR have better clinical outcomes than patients who do not achieve a CR with therapy. B-cell NHL is composed of multiple subtypes of neoplasm. These diseases are closely related to CLL in terms of natural history, biology, and responsiveness to similar therapeutic agents. These diseases are not usually cured by available chemotherapy and ultimately patients succumb to progression of resistant disease. Therefore, there is a need to develop better therapies to improve survival in patients with CLL and B-cell NHL.
Preclinical and clinical data suggests that pentostatin, bendamustine, ofatumumab are active drugs for the treatment of B-cell malignancies. In an earlier clinical trial conducted by Dr. Weiss (lead site PI), the combination of pentostatin and cyclophosphamide had very good activity in previously treated patients with B-cell neoplasms. This regimen was also better tolerated than similar fludarabine-based regimen. The response rates were improved with addition of rituximab, anti CD 20 antibody, to the above regimen. Studies have demonstrated synergy between bendamustine and purine analogs like pentostatin in killing cancer cell types of CLL and NHL. The combination of these three drugs (pentostatin, bendamustine and ofatumumab) has not been tested in clinical setting and we anticipate that the combination regimen will be more active than individual drugs alone. The aim of this trial is to find a safe dose of bendamustine to be used in combination with pentostatin and ofatumumab in patients with previously treated CLL and B-cell NHL.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01352312
|Contact: Mark Weiss, MD||215-955-8874|
|Contact: Clinical Research Management Office||215-955-1661|
|United States, Pennsylvania|
|Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Mark Weiss, MD 215-955-8874|
|Contact: Clinical Research Management Office 215-955-1661|
|Principal Investigator: Mark Weiss, MD|
|Sub-Investigator: Seyfettin Onder Alpdogan, MD|
|Sub-Investigator: Matthew Carabasi, MD|
|Sub-Investigator: Joanne Filicko-O'Hara, MD|
|Sub-Investigator: Neal Flomenberg, MD|
|Sub-Investigator: Dolores Grosso, DNP, CRNP|
|Sub-Investigator: Margaret Kasner, MD|
|Sub-Investigator: Lisa Kearns, CRNP|
|Sub-Investigator: John Wagner, MD|
|Sub-Investigator: Ubaldo Martinez-Outschoorn, MD|
|Sub-Investigator: Andrew Chapman, DO|
|Sub-Investigator: Barbara Pro, MD|
|Sub-Investigator: Manish Sharma, MD|
|Sub-Investigator: Thomas Klumpp, MD|
|Principal Investigator:||Mark Weiss, MD||Thomas Jefferson University|