Cladribine

Two single-center, open-label studies (Study A and Study B) of cladribine injection were conducted in patients with Hairy Cell Leukemia with evidence of active disease requiring therapy. 

Study A was conducted at the Scripps Clinic and Research Foundation, in which 89 patients received a single course of cladribine by continuous intravenous injection for 7 days at a dose of 0.09 mg/kg/day.

Study B was conducted at the M.D. Anderson Cancer Center in which 35 patients received a single course of cladribine by continuous intravenous injection for 7 days at a comparable dose of 3.6 mg/m²/day.

A complete response (CR) required clearing of the peripheral blood and bone marrow of hairy cells and recovery of the hemoglobin to 12 g/dL, platelet count to 100 x 10⁹/L, and absolute neutrophil count to 1,500 x 10⁶/L.  A good partial response (GPR) required the same hematologic parameters as a complete response, and that fewer than 5% hairy cells remain in the bone marrow.  A partial response (PR) required that hairy cells in the bone marrow be decreased by at least 50% from baseline and the same response for hematologic parameters as for complete response.  A pathologic relapse was defined as an increase in bone marrow hairy cells to 25% of pretreatment levels.  A clinical relapse was defined as the recurrence of cytopenias, specifically, decreases in hemoglobin ≥ 2 g/dL, ANC ≥ 25% or platelet counts ≥ 50,000.  Patients who met the criteria for a complete response but subsequently were found to have evidence of bone marrow hairy cells (< 25% of pretreatment levels) were reclassified as partial responses and were not considered to be complete responses with relapse.

Among 106 patients evaluable for efficacy, using the hematologic and bone marrow response criteria describe above, patients treated with cladribine injection demonstrated the following response rates for Study A and Study B, respectively:

Using an intent-to-treat analysis (n=123) and further requiring no evidence of splenomegaly as a criterion for CR (i.e., no palpable spleen on physical examination and ≤ 13 cm on CT scan), patients treated with cladribine injection demonstrated the following response rates for Study A and Study B, respectively:

The overall response rate for patients without prior chemotherapy was 92%, compared with 84% for previously treated patients.

After a reversible decline, normalization of peripheral blood counts (hemoglobin >12 g/dL, platelets >100 x 10⁹/L, absolute neutrophil count (ANC) >1,500 x 10⁶/L) was achieved by 92% of evaluable patients.  The median time to normalization of peripheral counts was 9 weeks from the start of treatment (Range: 2 to 72).  The median time to normalization of Platelet Count was two weeks, the median time to normalization of ANC was 5 weeks and the median time to normalization of Hemoglobin was 8 weeks. With normalization of Platelet Count and Hemoglobin, requirements for platelet and RBC transfusions were abolished after Months 1 and 2, respectively, in those patients with complete response.  Platelet recovery may be delayed in a minority of patients with severe baseline thrombocytopenia.  Corresponding to normalization of ANC, a trend toward a reduced incidence of infection was seen after the third month, when compared to the months immediately preceding cladribine injection therapy.