Case Studies

Not every patient within the indicated population will respond with Clolar, but the case studies below profile the use of Clolar in some heavily pretreated patients with acute lymphoblastic leukemia (ALL). For additional information on Clolar and case studies, please ask us for the Clolar Slide Kit.

Patient 1 profile

This patient is an 11-year-old Caucasian female diagnosed with ALL in June 1996 when she was 2 years old.

Patient 2 profile

This patient is a 12-year-old Black male diagnosed with pre-B cell ALL in September 2001 when he was 9 years old.

Patient 3 profile

This patient is an 18-year-old male, diagnosed with ALL in April 2000 when he was 13 years old.

Patient 1 profile

This patient is an 11-year-old Caucasian female diagnosed with ALL in June 1996 when she was 2 years old.

Standard induction 1

At that time, she received an induction regimen of prednisone, vincristine, and L-asparaginase with IT methotrexate, IT hydrocortisone, and IT cytarabine, followed by a post induction regimen of methotrexate, 6-mercaptopurine, and leucovorin, with IT methotrexate, IT hydrocortisone, and IT cytarabine with a response of complete remission.

Standard induction 2

After relapse in November 2000, she received a second induction regimen, consisting of decadron (HD), vincristine, L-asparaginase, and adriamycin with IT methotrexate, IT hydrocortisone, and IT cytarabine, followed by a post induction regimen of vincristine, etoposide, cytarabine, adriamycin, cytoxan, decadron, methotrexate, 6-mercaptopurine (HD), leucovorin, and PEG-asparaginase with IT methotrexate, IT hydrocortisone, and IT cytarabine with a response of complete remission.

A response with Clolar

• The patient relapsed again in November 2004, at which time she received 2 cycles of clofarabine 52 mg/m².
• She achieved a complete remission the following month (cycle 1).
• Grade 3 or 4 adverse events were: grade 3 allergic reaction, grade 3 influenza A infection, and two events of grade 3 febrile neutropenia.
• The patient underwent TBI and received a cord blood transplant from a matched, unrelated donor (4/6) in February 2005.
• The patient was alive as of last follow up in March 2005, with overall survival of 17+ weeks.

Patient 2 profile

This patient is a 12-year-old Black male diagnosed with pre-B cell ALL in September 2001 when he was 9 years old.

Standard induction 1

At that time, the patient received vincristine, prednisone, L-asparaginase, IT cytarabine, and IT methotrexate, with post induction therapy with vincristine, methotrexate, L-asparaginase, cyclophosphamide, dexamethasone, 6-thioguanine, cytarabine, 6-mercaptopurine, prednisone, doxorubicin, and IT methotrexate, and achieved a complete remission.

Standard induction 2

The patient relapsed in April 2004, however, and was treated with 1 cycle of vincristine, prednisone, L-asparaginase, daunomycin, IT cytarabine, IT methotrexate, and IT hydrocortisone, resulting in treatment failure.

Subsequent attempts at induction

• In May 2004, the patient received 1 cycle of cytarabine, etoposide, and L-asparaginase, resulting in treatment failure.
• In June 2004 he received 1 cycle of vincristine, methotrexate, IT methotrexate, IT cytarabine, and IT hydrocortisone resulting in treatment failure.
• Later that month he received 2 cycles of dexamethasone, cyclophosphamide, etoposide, IT methotrexate, IT hydrocortisone, and IT cytarabine, resulting in treatment failure.
• In August 2004 he received 1 cycle of vincristine, idarubicin, dexamethasone, L-asparaginase, IT methotrexate, IT cytarabine, and IT hydrocortisone, again resulting in treatment failure.

A response with Clolar

• In October 2004, after the 6th attempt at induction, the patient received 2 cycles of clofarabine. He achieved a complete remission without platelet recovery (after cycle 1).
• Grade 3 or 4 adverse events were: two events of grade 3 febrile neutropenia.
• The patient then received a cord blood transplant from an unrelated matched donor.
• He later passed away in July 2005 due to post-transplantation lymphoproliferative disorder.

Patient 3 profile

This patient is an 18-year-old male, diagnosed with ALL in April 2000 when he was 13 years old.

Standard induction 1

His first induction regimen was in May 2000 and consisted of daunoblastin, vincristine, dexamethasone, L-asparaginase, and methotrexate with IT methotrexate, IT cytarabine, and IT dexamethasone followed by a post induction regimen of vincristine, L-asparaginase, cytarabine, methotrexate and 6-mercaptopurine with IT methotrexate, IT cytarabine, and IT dexamethasone, for a best response of complete remission.

Standard induction 2

After a relapse three years later, he had a second induction regimen consisting of cyclophosphamide, mesna, dexamethasone, vincristine, doxorubicin, methotrexate, leucovorin, and cytarabine with IT methotrexate and IT cytarabine, and resulting in a partial response.

A response with Clolar

• In November 2004, the patient received 2 cycles of clofarabine 52 mg/m². He achieved a partial response in December. No grade 3 or 4 adverse events were reported.
• The patient underwent an allogenic peripheral blood bone marrow transplant later that month that was successfully engrafted in January.
• The patient was alive as of last follow-up one month post-transplant, with overall survival of 23+ weeks.

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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 Considerations

Clolar should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function, which is usually reversible and dose dependent, should be anticipated and is likely to increase the risk of infection, including severe sepsis. Administration of Clolar results in a rapid reduction in peripheral leukemia cells. Patients should be evaluated and monitored for signs and symptoms of tumor lysis syndrome and cytokine release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS)/capillary leak syndrome, and organ dysfunction. Clolar should be discontinued immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome, either of which can be fatal, and use of steroids, diuretics, and albumin considered.

The most common adverse effects after Clolar treatment, regardless of causality, were gastrointestinal tract symptoms, including vomiting (grade 3: 8%; grade 4: 1%), nausea (grade 3: 15%; grade 4: 1%), and diarrhea (grade 3: 10%); hematologic effects, including anemia (grade 3: 70%; grade 4: 18%), leukopenia (grade 4: 99%), thrombocytopenia (grade 3: 36%; grade 4: 64%), neutropenia (grade 3: 3%; grade 4: 7%), and febrile neutropenia (grade 3: 53%; grade 4: 3%); and infection (grade 3: 56%; grade 4: 18%).

Hepato-biliary toxicities were frequently observed in pediatric patients during treatment with Clolar. The most frequently reported cardiac disorder was tachycardia (34%), which was, however, already present in 27.4% of patients at study entry. Left ventricular systolic dysfunction was also noted. Since Clolar is excreted primarily by the kidneys, drugs with known renal toxicity should be avoided during the 5 days of Clolar administration. In addition, since the liver is a known target organ for Clolar toxicity, concomitant use of medications known to induce hepatic toxicity should also be avoided.

Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, have been observed in patients treated with Clolar. 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.

Pericardial effusion was a frequent finding in these patients on post-treatment studies. Careful hematologic monitoring during therapy is important. Hepatic and renal function should be assessed prior to and during treatment with Clolar, as the liver is a target organ for Clolar toxicity and the kidneys are the predominant mode of Clolar excretion.

Patients receiving Clolar may experience vomiting and diarrhea; they should therefore be advised regarding appropriate measures to avoid dehydration. Clolar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant and avoid breastfeeding while receiving treatment with Clolar.

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