Clofarabine
| Evidence Level: L1 | Predicted Indications: 8 |
Table of Contents
- Clofarabine
- Pharmacist Assessment Report
- Clofarabine: purine nucleoside analogue → myeloid leukemia
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Clofarabine: purine nucleoside analogue → myeloid leukemia
One-Sentence Summary
Clofarabine is a purine nucleoside analogue used as an anticancer agent that inhibits DNA synthesis. The TxGNN model predicts it may be effective for myeloid leukemia, with 43 clinical trials and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | myeloid leukemia |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L1 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the source record. From the published literature, clofarabine is a second-generation purine nucleoside analogue designed to combine the best qualities of fludarabine and cladribine. It inhibits ribonucleotide reductase and DNA polymerase, which depletes the pool of deoxynucleoside triphosphates needed for DNA replication, and it induces apoptosis.
These effects act on rapidly dividing leukemic blasts, regardless of whether they are lymphoid or myeloid in origin. This makes it mechanistically reasonable that a drug developed for lymphoblastic leukemia would also act on myeloid blasts. Clofarabine is already used in combination regimens for acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes, and a completed Phase 3 trial tested it directly in AML.
Clinical Trial Evidence
The data compiled for this report list 43 trials. The table shows the 10 most relevant.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02085408 | Phase 3 | Completed | 727 | Clofarabine induction and post-remission therapy vs. standard daunorubicin/cytarabine, then decitabine or observation, in older adults with newly diagnosed AML |
| NCT00317642 | Phase 3 | Completed | 326 | Double-blind comparison of clofarabine plus cytarabine vs. cytarabine alone in relapsed or refractory AML, age 55 and older |
| NCT00454480 | Phase 2/3 | Completed | 2000 | Treatment development programme for older patients with AML and high-risk MDS |
| NCT00044889 | Phase 2 | Completed | 40 | Single-arm study of clofarabine in adults with refractory or relapsed AML |
| NCT01295307 | Phase 2 | Completed | 86 | Clofarabine salvage therapy in relapsed or refractory AML |
| NCT00067028 | Phase 2 | Completed | 116 | Clofarabine with cytarabine and/or idarubicin in first relapse or refractory AML, high-grade MDS and myeloid blast-phase CML |
| NCT01193400 | Phase 2 | Terminated | 75 | Clofarabine and low-dose cytarabine induction and consolidation in AML patients aged 60 or older |
| NCT01643668 | Phase 2 | Completed | 34 | Reduced-intensity busulfan/clofarabine conditioning before allogeneic transplant (single-arm) |
| NCT00315705 | Phase 1/2 | Completed | 50 | Clofarabine with etoposide and cyclophosphamide in pediatric refractory or relapsed acute leukemias |
| NCT01160354 | Phase 1/2 | Terminated | 22 | Plerixafor plus clofarabine in older untreated AML; closed early |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22957815 | 2013 | Review | Leukemia & Lymphoma | Role of clofarabine in AML; mechanism and clinical activity |
| 25457773 | 2015 | Review | Critical Reviews in Oncology/Hematology | Clofarabine in adult AML, from monotherapy to combination strategies |
| 19852733 | 2009 | Review | Future Oncology | Single-agent activity compares favourably with standard antileukemic agents |
| 22170975 | 2012 | Review | Annals of Pharmacotherapy | Efficacy and tolerability in newly diagnosed AML in older adults |
| 16316309 | 2005 | Review | Expert Opinion on Pharmacotherapy | Clofarabine in AML and ALL |
| 21591997 | 2011 | Review | Expert Opinion on Investigational Drugs | Clofarabine for myelodysplastic syndromes |
| 36336258 | 2023 | Clinical study | Transplantation and Cellular Therapy | Clofarabine/busulfan myeloablative conditioning in active myeloid malignancies |
| 24081220 | 2014 | Case report | J Oncol Pharm Pract | Kidney toxicity in a patient with refractory AML treated with clofarabine |
| 27621503 | 2015 | Review | Hospital Pharmacy | Clofarabine and cytarabine regimen for AML |
| 17852710 | 2007 | Review | Leukemia & Lymphoma | Clofarabine past, present and future; three proposed mechanisms of action |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02330407 | CLOLAR | Not recorded | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (purine nucleoside analogue) |
| Myelosuppression Risk | High (neutropenia, anaemia and thrombocytopenia are expected with leukemia chemotherapy) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver and renal function (kidney toxicity has been reported in the literature) |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
- Conditions of concern: Safety screening data flag caution in liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, hyperbilirubinaemia (including Gilbert syndrome), kidney failure, uremia, hypotension, capillary leak syndrome, and fungal or other infectious diseases. These come from screening data, not from label text.
- Drug Interactions: 100 interactions were found, and the 20 listed in the data are all rated Moderate. Examples include amphotericin B (several formulations), clarithromycin, levofloxacin, kanamycin, neomycin, minocycline, bupropion, mesalazine, balsalazide, olsalazine, pioglitazone, acarbose, naltrexone, nicotinamide, nitisinone, clotrimazole and chenodeoxycholic acid.
- Reported toxicity: A published case report describes clofarabine-induced kidney toxicity in an adult with refractory AML.
Warnings and contraindications from the Canadian package insert are not yet available; please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two completed Phase 3 randomized trials (727 and 326 participants) tested clofarabine directly in AML, backed by many Phase 1/2 studies and several reviews. The drug’s high myelosuppression risk and the missing Canadian label safety data call for careful controls.
To proceed, the following is needed:
- Review of the Health Canada package insert for warnings and contraindications
- Detailed mechanism-of-action data from DrugBank
- Analysis of the Phase 3 trial outcomes (survival and remission rates) to confirm benefit over standard therapy
- A monitoring plan for myelosuppression, kidney and liver function, and interacting drugs, especially in older patients
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.