Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia

Abstract

BACKGROUND One of the mechanisms of action of cladribine is the inhibition of DNA repair of damage caused by radiation, alkylating agents, or other drugs. To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL). METHODS Twenty‐nine patients with refractory or recurrent CLL or PLL received cladribine 4 mg/m2/day and cyclophosphamide 350 mg/m2/day (both administered intravenously) for 3 days every 4 weeks. RESULTS Eleven patients (38%), nine with CLL and two with PLL, had a response. The median duration of response was 12 months. Severe extrahematologic toxicity (National Cancer Institute Grade 3–4) occurred in two patients, consisting of skin rash in one patient and progressive multifocal leukoencephalopathy in the other. The most common form of hematologic toxicity was severe neutropenia, which developed after 25% of the 84 courses was administered. Severe thrombocytopenia and anemia developed after 12% and 7% of the courses, respectively, and five episodes of anemia were immunomediated. In addition, three major infections resulted in the death of one patient. CONCLUSIONS Although inferior to the combination fludarabine plus cyclophosphamide, this regimen showed interesting activity in patients with advanced CLL or PLL. Myelosuppression was the major dose‐limiting toxic effect. Cancer 2003;97:114–20. © 2003 American Cancer Society. DOI 10.1002/cncr.11000

Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment

“…Pentostatin regimens may be given in a single day, making them more convenient than the multiday infusions of fludarabine, and they may have less myelosuppression than fludarabine. Cladribine has been studied in several small trials [37][38][39][40]. Clofarabine (Clolar ® ; Genzyme Oncology, Cambridge, MA, http://www.genzyme.com) is a newly approved nucleoside analogue indicated for the treatment of pediatric leukemia; trials are ongoing to determine its efficacy in CLL.…”

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: Impact of novel therapies

“…Another explanation could be that the association between Hodgkin disease and PML is already well known and therefore not worth reporting. In contrast, after 1990, its appears that LPDs-associated PML is largely restricted to two groups of severely T-cell immunosuppressed patients: B-CLL patients who had received purine analogues [30,33,[35][36][37][39][40][41][42][46][47][48] and heavily pretreated patients with aggressive non-Hodgkin lymphoma after HDT/HSCT [29,31,34,[43][44][45]49].…”

“…All the patients in group A were diagnosed by histology (85% at autopsy). In group B, exclusive histologic diagnosis was made only in 16 patients (66.6%): 4 patients (16.6% of the total) were diagnosed at autopsy and 12 (50% of the total) by using stereotactic brain biopsy) [30][31][32][33][34][35][36][37][38][39]43,46,47]. The remaining 8 group B patients (33.3%) were diagnosed by clinical and/or neuroradiological criteria and the presence of a positive PCR for JC viral DNA in the CSF (Table I) [40][41][42]44,45,48,49].…”

“…The increase in the number of PML cases reported since 1990 in patients treated either with purine analogues [30,33,[35][36][37][39][40][41][42][46][47][48] or with HDT/ HSCT [29,31,34,[43][44][45]49], and their peculiar char- acteristics have led us to analyze these groups separately. Of the 24 PML patients reported since 1990, 14 had received purine analogues (10 fludarabine as single agent, 1 patient cladribine plus cyclophosphamide, and 3 fludarabine plus an alkylating agent), with a median number of 5.5 courses (range 1-12).…”

A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia

“…Nevertheless, CR was achieved in only a few cases [6][7][8]. In different studies, the purine nucleoside analogues Fludarabine, Cladribine or Pentostatin, used alone, allowed achieving CR in 0% to 11% of the cases and PR in 11% to 60% [7,9]. CR has also been reported with the monoclonal antibodies Alemtuzumab and Rituximab [10][11][12].…”