Phase I/II Study of the Combination of Bendamustine, Rituximab and Pixantrone in Patients With Relapsed/Refractory B Cell Non-Hodgkin's Lymphoma
1. Part I: Subjects must have relapsed or refractory B cell NHL;
2. Part II: Subjects must have relapsed or refractory aggressive B cell NHL including
follicular lymphoma (FL) grade 3, Diffuse Large B Cell Lymphoma (DLBCL), transformed
NHL, mantle cell lymphoma (MCL), or other aggressive B cell NHL histology as per the
WHO 2008 criteria;
3. Refractory disease (defined as persistence of evaluable disease after therapy) or
relapsed disease following at least one prior treatment regimen that should include
autologous stem cell transplant unless a patient was not eligible or refused prior
4. Age ≥ 18 years old;
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2;
6. Subjects must have measurable or evaluable disease based on physical exam and/or
radiographs (CT, MRI, PET) or bone marrow involvement;
7. Female subject is either post-menopausal or surgically sterilized;
8. Laboratory Values:
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L; lower levels accepted if due to
marrow involvement by lymphoma
- Platelets ≥ 75,000/mcl; lower levels accepted if due to marrow involvement by
- Total bilirubin ≤ 1.5 X institutional upper limit of normal; ≤ 3.0 ULN accepted
in subjects with Gilbert's Syndrome
- AST/ALT ≤ 1.5 X institutional upper limit of normal. Subjects with known liver
involvement by lymphoma: AST/ALT ≤ 2 X institutional upper limit of normal
- Serum creatinine < 1.5 X institutional upper limit of normal
9. Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed
1. No chemotherapy, radiation, biologics or immunotherapy within 2 weeks prior to
registration (6 weeks if last received BCNU or mitomycin C).
2. No radioimmunotherapy within 2 months prior to registration.
3. Subjects receiving chronic, systemic treatment with corticosteroids equivalent to >
20mg of prednisone per day. Subjects receiving replacement for adrenal insufficiency
will be allowed on the study. Topical or inhaled corticosteroids are allowed.
4. Subjects with a history of another primary malignancy ≤ 3 years ago, with the
exception of inactive basal, squamous cell carcinoma of the skin or superficial
melanoma only requiring excision, prostate cancer with a PSA that has not increased
for at least 3 months, carcinoma in situ of the cervix.
5. Major surgery ≤ 4 weeks prior to registration. Minor surgery ≤ 2 weeks prior to
registration. Insertion of a vascular access device is not considered major or minor
surgery. Subjects must have recovered from all surgery related toxicities to ≤ grade
1 or to baseline if subject started with > grade 1 toxicity, not otherwise violating
the above inclusion criteria.
6. Subjects who have received investigational drugs ≤ 4 weeks prior to registration.
7. Impaired Cardiac Function:
- QTc > 480 on screening ECG.
- Previous history of angina pectoris or acute MI within 6 months
- Congestive heart failure (New York Heart Association functional classification
III-IV) or baseline MUGA/ECHO shows LVEF < 45%
- Any history of torsade de pointes, ventricular fibrillation, uncontrolled
ventricular tachycardia, or uncontrolled atrial fibrillation.
8. Female patients who are pregnant or breastfeeding
9. Patients with history of untreated hepatitis B or who are known carriers of hepatitis
B will be excluded from this trial. All subjects will be screened prior to study
10. Concurrent use of other anti-cancer agents or anti-cancer treatments.