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Leustatin (Cladribine) - Summary



LEUSTATIN (cladribine) Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. Serious neurological toxicity (including irreversible paraparesis and quadraparesis) has been reported in patients who received LEUSTATIN Injection by continuous infusion at high doses (4 to 9 times the recommended dose for Hairy Cell Leukemia). Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard cladribine dosing regimens.

Acute nephrotoxicity has been observed with high doses of LEUSTATIN (4 to 9 times the recommended dose for Hairy Cell Leukemia), especially when given concomitantly with other nephrotoxic agents/therapies.



For Intravenous Infusion Only

LEUSTATIN (cladribine) Injection (also commonly known as 2-chloro-2'-deoxy-(beta)-D-adenosine) is a synthetic antineoplastic agent for continuous intravenous infusion.

LEUSTATIN Injection is indicated for the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms.

See all Leustatin indications & dosage >>


Published Studies Related to Leustatin (Cladribine)

Reduction in Healthcare and Societal Resource Utilization Associated with Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis: Analysis of Economic Data from the CLARITY Study. [2012.01.01]
Background: Multiple sclerosis (MS) is a common, chronic, neurodegenerative condition associated with substantial healthcare and societal economic burden... Conclusion: This study provides evidence that the efficacy of cladribine tablets observed during the CLARITY study was associated with a reduced consumption of healthcare resources and a decreased need for medical and societal support.

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. [2011.05]
BACKGROUND: Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. OBJECTIVE: To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS... CONCLUSION: The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.

Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study). [2010.04.10]
PURPOSE Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL...

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. [2010.02.04]
BACKGROUND: Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis... CONCLUSIONS: Treatment with cladribine tablets significantly reduced relapse rates, the risk of disability progression, and MRI measures of disease activity at 96 weeks. The benefits need to be weighed against the risks. (ClinicalTrials.gov number, NCT00213135.) 2010 Massachusetts Medical Society

Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG). [2010.02]
OBJECTIVES: The addition of cladribine to the standard regimen consisting of daunorubicin and cytarabine has been reported to increase the efficacy of induction therapy in acute myeloid leukemia (AML). The goal of this study was to determine the effect of this modification on the incidence and spectrum of infectious complications... CONCLUSIONS: The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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Clinical Trials Related to Leustatin (Cladribine)

2-Chlorodeoxyadenosine and Cytarabine in Patients With Idiopathic Hypereosinophilic Syndrome (HES) [Active, not recruiting]
Primary Objectives:

1. To determine the response rate, progression-free survival (PFS) and overall survival of patients who receive 2-CdA + Ara-C.

2. To examine if there is any clonality in the cytokine expression of helper T cells or cytokine receptor expression of eosinophils.

3. To determine the effect of 2-CdA on accumulation of Ara-C triphosphate in eosinophils.

Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia [Recruiting]

Hairy cell leukemia (HCL) is highly responsive to but not curable by cladribine (CdA). HCL responds to rituximab, which is not yet standard therapy for HCL.

Patients with the CD25-negative variant (HCLv) respond poorly to initial cladribine but do respond to rituximab in anecdotal reports.

Deoxycytidine kinase phosphorylates cladribine to CdATP, which incorporates into DNA, leading to DNA strand breaks and inhibition of DNA synthesis. Rituximab is an anti-CD20 monoclonal antibody which induces apoptosis and either complement or antibody dependent cytotoxicity (ADCC or CDC).

Patients in complete remission (CR) to cladribine have minimal residual disease (MRD) by immunohistochemistry of the bone marrow biopsy (BMBx IHC), a risk for early relapse. Tests for HCL MRD in blood or marrow include flow cytometry (FACS) or PCR using consensus primers. The most sensitive HCL MRD test is real-time quantitative PCR using sequence-specific primers (RQ-PCR).

In studies with limited follow-up, MRD detected by tests other than RQ-PCR can be eliminated by rituximab after cladribine in greater than 90 percent of patients, but MRD rates after cladribine alone are unknown. Simultaneous cladribine and rituximab might be superior or inferior to delaying rituximab until detection of MRD.

Only 4 HCL-specific trials are listed on Cancer. gov: a phase II trial of cladribine followed 4 weeks later by 8 weekly doses of rituximab, and phase I-II trials of recombinant immunotoxins targeting CD22 (BL22, HA22) and CD25 (LMB-2).



To determine if HCL MRD differs at 6 months after cladribine with or without rituximab administered concurrently with cladribine.


- To compare cladribine plus rituximab vs cladribine alone in terms of 1) initial

MRD-free survival and disease-free survival, and 2) response to delayed rituximab for relapse, to determine if early rituximab compromises later response.

- To determine if MRD levels and tumor markers (soluble CD25 and CD22) after cladribine

and/or rituximab correlate with response and clinical endpoints.

- To determine, using MRD and tumor marker data, when BMBx can be avoided.

- To compare response and MRD after the 1st and 2nd courses of cladribine.

- To evaluate the effects of cladribine and rituximab on normal T- and B-cells.

- To enhance the study of HCL biology by cloning, sequencing and characterizing

monoclonal immunoglobulin rearrangements.


HCL with 0-1 prior courses of cladribine and treatment indicated.


Cladribine 0. 15 mg/Kg/day times 5 doses each by 2hr i. v. infusion (days 1-5)

Rituximab 375 mg/m2/week times 8 weeks, randomized half to begin day 1, then repeat for all patients with blood-MRD relapse at least 6 months after cladribine. Also may repeat for those with blood-MRD relapse at least 6 months after delayed rituximab.

MRD tests used for the primary objective will be limited to BMBx IHC, blood FACS or blood consensus PCR, all CLIA certified. Blood MRD relapse is defined as FACS positivity or low blood counts (ANC less than 1500/microl, Plt less than 100,000/microl, or Hgb less than 11).

Stratification: 68 patients with 0 and 62 with 1 prior course of cladribine.

Statistics: 80% power to discriminate rates of MRD of 5 vs 25%, or 10 vs 35%

Non-randomized arm: 20 with HCLv will begin rituximab with cladribine.

Accrual Ceiling: 152 patients (130 HCL, 2 extra HCL if needed, and 20 HCLv.)

Treatment of Macroglobulinemic Lymphoma With 2CdA, Cyclophosphamide and Rituximab [Active, not recruiting]
Primary Objectives:

1. To assess frequency and complete response in newly diagnosed patients with Waldenstrom's macroglobulinemia treated with 2CdA, cyclophosphamide and rituximab.

2. To assess duration of unmaintained remission and frequency of recontrol with resumption of treatment.

CLARITY - Safety and Efficacy of Oral Cladribine in Subjects With Relapsing-Remitting MS [Active, not recruiting]

Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, or Relapsed B-Cell Non-Hodgkin Lymphoma [Recruiting]
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving vorinostat together with cladribine and rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with cladribine and rituximab and to see how well it works in treating patients with mantle cell lymphoma, chronic lymphocytic leukemia, or relapsed B-cell non-Hodgkin lymphoma.

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Reports of Suspected Leustatin (Cladribine) Side Effects

Blood Creatinine Increased (5)Rash (5)Drug Ineffective (3)Chills (3)Pyrexia (3)Myalgia (3)Liver Function Test Abnormal (3)Pancytopenia (3)Tremor (3)Flushing (3)more >>

Page last updated: 2011-12-09

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