Important Safety Information
Clolar® should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. View additional Important Safety Information.

Adverse Events

In clinical trials, 115 pediatric patients with ALL (70) or AML (45) received the recommended dose of Clolar 52 mg/m2 daily × 5. There was no dose escalation.

In these patients, the most common adverse reactions (≥10%) with Clolar: nausea (73%) vomiting (78%), diarrhea (56%), febrile neutropenia (55%), headache (43%), rash (38%), pruritus (43%), pyrexia (39%), fatigue (34%), palmar-plantar erythrodysesthesia syndrome (16%), anxiety (21%), flushing (19%), and mucosal inflammation (16%). (See Table 1 for a list of the most commonly reported adverse reactions.)

Table 1:  Most commonly reported (≥5%) adverse reactions by System Organ Class (SOC)*


Total (N=115)Grade 3‡Grade 4‡Grade 5‡
System Organ Class†Preferred Term† n (%) n (%) n (%) n (%)
Blood and lymphatic system disorders Febrile neutropenia 63 (55) 59 (51) 3 (3) .
Neutropenia 11 (10) 3 (3) 8 (7) .
Cardiac disorders Pericardial effusion 9 (8) . 1 (1) .
Tachycardia 40 (35) 6 (5) . .
Gastrointestinal disorders Abdominal pain 40 (35) 8 (7) . .
Abdominal pain upper 9 (8) 1 (1) . .
Diarrhea 64 (56) 14 (12) . .
Gingival bleeding 16 (14) 7 (6) 1 (1) .
Mouth hemorrhage 6 (5) 2 (2) . .
Nausea 84 (73) 16 (14) 1 (1) .
Oral mucosal petechiae 6 (5) 4 (4) . .
Proctalgia 9 (8) 2 (2) . .
Stomatitis 8 (7) 1 (1) . .
Vomiting 90 (78) 9 (8) 1 (1) .
General disorders and administration site conditions Asthenia 12 (10) 1 (1) 1 (1) .
Chills 39 (34) 3 (3) . .
Fatigue 39 (34) 3 (3) 2 (2)
Irritability 11 (10) 1 (1) . .
Mucosal inflammation 18 (16) 2 (2) . .
Edema 14 (12) 2 (2) . .
Pain 17 (15) 7 (6) 1 (1) .
Pyrexia 45 (39) 16 (14) . .
Hepatobiliary disorder Jaundice 9 (8) 2 (2) . .
Infections and infestations Bacteremia 10 (9) 10 (9) . .
Candidiasis 8 (7) 1 (1) . .
Catheter-related infection 14 (12) 13 (11) . .
Cellulitis 9 (8) 7 (6) . .
Clostridium colitis 8 (7) 6 (5) . .
Herpes simplex 11 (10) 6 (5) . .
Herpes zoster 8 (7) 6 (5) . .
Oral candidiasis 13 (11) 2 (2) . .
Pneumonia 11 (10) 6 (5) 1 (1) 1 (1)
Sepsis 11 (10) 5 (4) 2 (2) 4 (3.5)
Septic shock 8 (7) 1 (1) 2 (2) 5 (4.4)
Staphylococcal bacteremia 7 (6) 5 (4) 1 (1) .
Staphylococcal sepsis 6 (5) 5 (4) 1 (1) .
Upper respiratory tract infection 6 (5) 1 (1) . .
Metabolism and nutrition disorders Anorexia 34 (30) 6 (5) 8 (7) .
Musculoskeletal and connective tissue disorders Arthralgia 10 (9) 3 (3) . .
Back pain 12 (10) 3 (3) . .
Bone pain 11 (10) 3 (3) . .
Myalgia 16 (14) . . .
Pain in extremity 34 (30) 6 (5) . .
Neoplasms benign, malignant, and unspecified (incl. cysts and polyps) Tumor lysis syndrome 7 (6) 7 (6) . .
Nervous system disorders Headache 49 (43) 6 (5) . .
Lethargy 12 (10) 1 (1) . .
Somnolence 11 (10) 1 (1) . .
Psychiatric disorders Agitation 6 (5) 1 (1) . .
Anxiety 24 (21) 2 (2) . .
Renal and urinary disorders Hematuria 15 (13) 2 (2) . .
Respiratory, thoracic, and mediastinal disorders Dyspnea 15 (13) 6 (5) 2 (2) .
Epistaxis 31 (27) 15 (13) . .
Pleural effusion 14 (12) 4 (4) 2 (2) .
Respiratory distress 12 (10) 5 (4) 4 (4) 1 (1)
Tachypnea 10 (9) 4 (4) 1 (1) .
Skin and subcutaneous tissue disorders Erythema 13 (11) . . .
Palmar-plantar erythrodysesthesia syndrome 18 (16) 8 (7) . .
Petechiae 30 (26) 7 (6) . .
Pruritus 49 (43) 1 (1) . .
Rash 44 (38) 8 (7) . .
Rash pruritic 9 (8) . . .
Vascular disorders Flushing 22 (19) . . .
Hypertension 15 (13) 6 (5) . .
Hypotension 33 (29) 13 (11) 9 (8) .

* Pooled analysis of 115 pediatric patients with ALL or AML who received the recommended dose of Clolar (52 mg/m2/day I.V. x 5 days).
† Patients with more than 1 preferred term within a System Organ Class are counted only once in the System Organ Class totals. Patients with more than 1 occurrence of the same preferred term are counted only once within that term and at the highest severity grade.

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Prescribing Information

Prescribing Information 
Clolar prescribing information (.pdf)

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Indication

Clolar is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

Important Safety Information

Warnings and Precautions:

Clolar® should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.

    Hematologic Toxicity

    • Monitor complete blood counts and platelet counts during and after Clolar therapy.
    • Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, has been observed in patients treated with Clolar. At initiation of treatment, most patients in the clinical studies had hematological impairment as a manifestation of leukemia.
    • Because of the pre-existing immunocompromised condition of these patients and prolonged neutropenia that can result from treatment with Clolar, patients are at increased risk for severe opportunistic infections.

    Infections

    The use of Clolar is likely to increase the risk of infection, including severe sepsis, as a result of bone marrow suppression. Monitor patients for signs and symptoms of infection and treat promptly.

      Hyperuricemia (Tumor Lysis)

      Administration of Clolar may result in a rapid reduction in peripheral leukemia cells. Evaluate and monitor patients undergoing treatment for signs and symptoms of tumor lysis syndrome. Provide intravenous infusion fluids throughout the five days of Clolar administration to reduce the effects of tumor lysis and other adverse events. Administer allopurinol if hyperuricemia (tumor lysis) is expected.

        Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome

        • Evaluate and monitor patients undergoing treatment with Clolar for signs and symptoms of cytokine release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS), capillary leak syndrome and organ dysfunction.
        • Discontinue Clolar immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome, either of which can be fatal, and consider use of steroids, diuretics, and albumin. Re-institute Clolar when the patient is stable, generally with a 25% dose reduction. The use of prophylactic steroids may be of benefit in preventing signs and symptoms of cytokine release.

        Hepatic Enzymes

        Hepato-biliary enzyme elevations were frequently observed in pediatric patients during treatment with Clolar. Some patients discontinued treatment due to hepatic enzyme abnormalities.

          Hepatic and Renal Impairment

          • Clolar has not been studied in patients with hepatic or renal dysfunction. Its use in such patients should be undertaken only with the greatest caution.
          • Patients who have previously received a hematopoietic stem cell transplant (HSCT) may be at higher risk for hepatotoxicity suggestive of veno-occlusive disease (VOD) following treatment with clofarabine (40 mg/m2) when used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2). Severe hepatotoxic events have been reported in an ongoing Phase 1/2 combination study of clofarabine in pediatric patients with relapsed or refractory acute leukemia.

          Use in Pregnancy

          Clolar can cause fetal harm when administered to a pregnant woman. Intravenous doses of clofarabine in rats and rabbits administered during organogenesis caused an increase in resorptions, malformations, and variations. Women of childbearing potential should be advised to avoid becoming pregnant while receiving Clolar.

            Nursing Mothers

            Female patients should be advised to avoid breast-feeding during treatment with Clolar.

              Incidence of Treatment Emergent Laboratory Abnormalities (All Grades)

              ParameterAny gradeGrade 3 or higher
              Anemia 83% 75%
              Leukopenia 88% 88%
              Lymphopenia 82% 82%
              Neutropenia 64% 64%
              Thrombocytopenia 81% 80%
              Elevated creatinine 50% 8%
              Elevated SGOT 74% 36%
              Elevated SGPT 81% 43%
              Elevated total bilirubin 45% 13%

              Adverse Reactions:

              Most common adverse reactions with Clolar were nausea (73%), vomiting (78%), diarrhea (56%), febrile neutropenia (55%), headache (43%), rash (38%), pruritus (43%), pyrexia (39%), fatigue (34%), palmar-plantar erythrodysesthesia syndrome (16%), anxiety (21%), flushing (19%), and mucosal inflammation (16%).

              For more information, please consult the full Prescribing Information (PDF).