Clinical trial NCT01076556 (phase 1, status: terminated)
Conditions: chronic lymphocytic leukemia, prolymphocytic leukemia, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, stage i chronic lymphocytic leukemia, stage i small lymphocytic lymphoma, stage ii chronic lymphocytic leukemia, stage ii small lymphocytic lymphoma, stage iii chronic lymphocytic leukemia, stage iii small lymphocytic lymphoma, stage iv chronic lymphocytic leukemia, stage iv small lymphocytic lymphoma
ICD codes: C91.11, C91.12, C91.10, C91.31, C91.32, C91.61, C91.62, C91.30, C91.60, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, A87.2, K52.832, D72.111, C91.11, C91.12, C91.10, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: alvocidib hydrochloride, cyclophosphamide
SMILES: CN1CC[C@@H]([C@H](O)C1)C1=C(O)C=C(O)C2=C1OC(=CC2=O)C1=CC=CC=C1Cl, ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic
             leukemia* (PLL) arising from CLL

               -  Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point
                  since initial diagnosis of CLL

               -  Patients must have B-cells that co-express CD5 with CD19 or CD20

               -  Patients who do not have dim sIg or CD23 expression on their leukemia cells
                  should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle
                  cell lymphoma

          -  To be considered high risk, patients must meet the following criteria:

               -  At least 1 of the following:

                    -  17p deletion

                    -  11q deletion

                    -  Un-mutated IgV_H (≥ 98% homology)

                    -  Age > 70 years

                    -  B_2M > 4

               -  AND at least 1 of the following:

                    -  Progressive or marked splenomegaly and/or lymphadenopathy

                    -  Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/mm^3)

                    -  Weight loss exceeding 10% of body weight over preceding 6 months

                    -  NCI grade 2 or 3 fatigue

                    -  Fevers > 100.5° F or night sweats for > 2 weeks without evidence of
                       infection

                    -  Progressive lymphocytosis, with an increase exceeding 50% over a 2-month
                       period or a doubling time of < 6 months

          -  No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for
             new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for
             diabetes)

               -  No requirement for chronic corticosteroids

          -  ECOG performance status 0-2

          -  Creatinine ≤ 2.0 mg/dL

          -  Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease
             infiltration of the liver

          -  AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver

          -  Negative pregnancy test

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  No secondary or other malignancy that will limit survival to < 2 years

          -  No uncontrolled concurrent illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness or social situations that would limit compliance with study
                  requirements

          -  No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication

          -  No active hepatitis B infection

          -  No known G6PD deficiency

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used
             in this study

          -  No prior alvocidib

          -  No prior purine analog therapy

          -  No more than 1 prior treatment with a biologic or alkylating agent

          -  No other concurrent investigational agents