Status:
COMPLETED
BR in Patients With CLL With Comorbidities and/or Renal Dysfunction
Lead Sponsor:
Dartmouth-Hitchcock Medical Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This is a non-randomized, open label, dose-ranging study of Bendamustine and Rituximab (BR) in patients with previously untreated or relapsed/refractory Chronic Lymphocytic Leukemia (CLL) who have mul...
Detailed Description
This is a non-randomized open label dose-ranging study of Bendamustine and Rituximab (BR) in patients with previously untreated or relapsed/refractory CLL who have multiple comorbidities (Cumulative I...
Eligibility Criteria
Inclusion
- Patients must have histologically or flow cytometry confirmed diagnosis of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) according to NCI-WG 1996 guidelines (41). The malignant B cells must co-express CD5 with CD19 or CD20. Patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma.
- Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment:
- A minimum of any one of the following constitutional symptoms:
- Unintentional weight loss \>10% within the previous 6 months prior to screening.
- Extreme fatigue (unable to work or perform usual activities).
- Fevers of greater than 100.5 F for ≥2 weeks without evidence of infection.
- Night sweats without evidence of infection.
- Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia.
- Massive (ie, \>6 cm below the left costal margin), progressive or symptomatic splenomegaly.
- Massive nodes or clusters (ie, \> 10 cm in longest diameter) or progressive lymphadenopathy.
- Progressive lymphocytosis with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months.
- Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids.
- Prior treatment: Patients have not had prior treatment of CLL OR Previously treated relapsed CLL patients must have received not more than 3 prior therapies for CLL. Prior bendamustine and rituximab are allowed.
- Patients must have ECOG performance status 0-3.
- Patients must have a Cumulative Illness Risk Score \[CIRS\]≥7 with at least one grade 3-4 category \[CLL will not be considered a comorbidity\]; or estimated creatinine clearance (CrCL) using the Cockcroft-Gault equation ≥15 mL/min but ≤40 ml/min (Appendix 1: CCI Criteria).
- Patients must have organ function as defined below:
- direct bilirubin ≤2 X institutional ULN (unless due to known Gilbert's syndrome or compensated hemolysis directly attributable to CLL)
- AST or ALT \< 2.5 X institutional ULN
- estimated CrCL using the Cockcroft-Gault equation ≥15 mL/min.
- Absolute neutrophil count (ANC) ≥500/mm3 independent of growth factor support;
- platelets ≥30,000/mm3 independent of transfusion support with no active bleeding.
- Ability to understand and the willingness to sign a written informed consent document.
- Women of childbearing potential must have a negative serum human chorionic gonadotropin or urine pregnancy test at screening.
- All patients of reproductive potential (heterosexually active men and women) must agree to a use of a barrier method of contraception and a second method of contraception and men must agree not to donate sperm during the study and for 3 months after receiving the last dose of study treatment.
Exclusion
- Recent therapeutic intervention including a) prior nitrosoureas or mitomycin C within 6 weeks; b) therapeutic anticancer antibodies (including rituximab) within 4 weeks; c) radio- or toxin-immunoconjugates within 10 weeks; d) all other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy.
- Inadequate recovery from adverse events related to prior therapy to grade ≤1 (excluding Grade 2 alopecia and neuropathy).
- Bendamustine-refractory (no response to a regimen containing bendamustine) or relapse following treatment with a bendamustine-containing regimen within 6 months of treatment with that regimen.
- Chronic use of corticosteroids in excess of prednisone 20 mg/day or its equivalent or chronic use of other immunosuppressive agents (azathioprine, methotrexate, tacrolimus, cyclosporine). Stem cell transplant recipients must have no evidence of active graft-versus-host disease.
- History of prior malignancy except: a) Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study; b) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c) adequately treated in situ carcinomas (eg, cervical, esophageal, etc.) without evidence of disease; d) asymptomatic prostate cancer managed with "watch and wait" strategy.
- Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis is not an exclusion).
- Known Richter's transformation.
- Advanced renal failure (estimated CrCL \< 15 mL/min) or on dialysis.
- Human Immunodeficiency Virus (HIV) or Hepatitis C antibody positivity, or active hepatitis B.
- Major surgery (requiring general anesthesia) within 30 days prior to initiation of therapy.
- Uncontrolled bacterial, viral, or fungal infection.
- Inability to adhere to the study schedule or the required follow-up.
Key Trial Info
Start Date :
April 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 28 2016
Estimated Enrollment :
8 Patients enrolled
Trial Details
Trial ID
NCT01832922
Start Date
April 1 2013
End Date
November 28 2016
Last Update
March 30 2018
Active Locations (2)
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1
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
2
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03750