Nelarabine

From discovery to approval

1. c. 1983 · Earliest report found

   A 2017 review says arabinosylguanine (ara-G) was developed after observations in purine nucleoside phosphorylase deficiency, and nelarabine as its water-soluble prodrug. The earliest paper found on ara-G is from 1983; the first report of nelarabine itself was not found.^[2][3][4]

2. 2005-10-28 · FDA accelerated · 22 years after first description

   Treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Approved under the accelerated approval regulations (21 CFR 314.510). The letter's postmarketing commitment was to submit the results of the proposed phase III COG trial AALL0434 to demonstrate clinical benefit.^[5]

3. 2007-08-22 · EMA exceptional · 24 years after first description

   Atriance, marketing authorisation issued 22 August 2007 according to the EPAR page, which states it was authorised under exceptional circumstances. The page lists treatment of T-cell acute lymphoblastic leukaemia and T-cell lymphoblastic lymphoma not responding to, or relapsed after, at least two chemotherapy regimens (the page shows the current text).^[6]

4. 2019-07-31 · FDA converted · 36 years after first description

   Prior Approval supplement providing the AALL0434 data that address PMR 1284-1, with labeling changes (clarified age range in section 1, neurotoxicity, AALL0434 safety results, pediatric experience). Under the heading 'Subpart H fulfilled' the letter states that the NDA was approved under 21 CFR 314 Subpart H (accelerated approval) and that approval of this supplement fulfills the commitments made under 21 CFR 314.510. The letter does not itself use the word 'converted' or 'regular'. FDA's list 'Verified Clinical Benefit | Cancer Accelerated Approvals' (opened 20 October 2026) records Arranon (nelarabine) for relapsed or refractory T-cell ALL with an accelerated approval date of 10/28/2005 and a traditional approval date of 7/31/2019, which supports the type 'converted'.^[7]

How it works

Nelarabine is demethylated by adenosine deaminase to ara-G, which is phosphorylated to ara-GTP. Accumulation of ara-GTP in leukaemic blasts allows its incorporation into DNA, inhibiting DNA synthesis and causing cell death.^[1]

Where it came from and why

The 1983 paper reports that arabinosylguanine, resistant to cleavage by purine nucleoside phosphorylase, was more potent than deoxyguanosine in T-leukaemic cells and kept selective toxicity for them. A 1985 study found it 70-fold more inhibitory to T- than B-lymphoblasts.

Cancers

• Relapsed or refractory T-cell leukaemia and lymphoblastic lymphoma

  A Children's Oncology Group phase II study enrolled 121 patients; complete plus partial response rates at the final doses were 55% in first bone marrow relapse, 27% in later relapse, 33% with CSF involvement and 14% in extramedullary relapse.^[8]

• Newly diagnosed T-cell acute lymphoblastic leukaemia

  In the randomised phase III AALL0434 trial, adding six five-day courses of nelarabine was associated with 5-year disease-free survival of 88.2% versus 82.1% without it (P = .029).^[9]

Worth knowing

• In AALL0434, patients who received nelarabine had fewer isolated and combined CNS relapses (1.3% versus 6.9%; P = .0001).^[9]
• The most significant adverse events in the phase II study in children and young adults were neurologic: 31 episodes of grade 3 or worse in 27 patients (18%).^[8]
• A 2003 laboratory study reports that T-lymphoblast cells accumulated the highest ara-GTP levels and were the most sensitive to ara-G-induced apoptosis compared with B-lineage and myeloid cell lines.^[10]
• The EMA page says Atriance was authorised under exceptional circumstances because the diseases are rare, and notes that the supporting information rests on limited data.^[6]

On this site

• 2005 Nelarabine for T-cell ALL

References

1. Sandoz Inc. Arranon (nelarabine): prescribing information. DailyMed, set ID 0f9051de-5c4d-4c0f-8c19-e15214498cca, published 23 March 2026. Read 26 October 2026. Source
2. Kadia TM, Gandhi V. Nelarabine in the treatment of pediatric and adult patients with T-cell acute lymphoblastic leukemia and lymphoma. Expert Rev Hematol. 2017;10(1):1-8. PubMedDOI
3. Cohen A, Lee JW, Gelfand EW. Selective toxicity of deoxyguanosine and arabinosyl guanine for T-leukemic cells. Blood. 1983;61(4):660-6. PubMed
4. Shewach DS, Daddona PE, Ashcraft E, Mitchell BS. Metabolism and selective cytotoxicity of 9-beta-D-arabinofuranosylguanine in human lymphoblasts. Cancer Res. 1985;45(3):1008-14. PubMed
5. US Food and Drug Administration. Approval letter, Arranon (nelarabine) injection, NDA 21-877, GlaxoSmithKline. Electronic signature date 28 October 2005. Source
6. European Medicines Agency. Atriance (nelarabine): European public assessment report page (authorised under exceptional circumstances; marketing authorisation issued 22/08/2007). Read 26 October 2026. Source
7. US Food and Drug Administration. Supplement approval letter (fulfillment of postmarketing requirement), Arranon (nelarabine) injection, NDA 021877/S-010, Novartis Pharmaceuticals Corporation. Electronic signature date 31 July 2019. Source
8. Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005;23(15):3376-82. PubMedDOI
9. Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, et al. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020;38(28):3282-3293. PubMedDOI
10. Rodriguez CO Jr, Stellrecht CM, Gandhi V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood. 2003;102(5):1842-8. PubMedDOI