Haematology-Oncology · Clinical trials
Acute Lymphoblastic Leukaemia (ALL) Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About acute lymphoblastic leukaemia (all) — and why its trials are hard
Acute lymphoblastic leukaemia is an aggressive malignancy of immature lymphoid precursors (most commonly B-cell) that flood the marrow and blood, causing rapid marrow failure. It is the commonest childhood cancer, where intensive multi-agent chemotherapy cures the large majority, but outcomes in adults and in relapsed/refractory disease are markedly worse. Risk stratification relies on immunophenotype, cytogenetics/molecular lesions (notably BCR-ABL1 in Philadelphia-chromosome-positive disease) and minimal residual disease (MRD) response, which is the single most powerful prognostic factor. Immunotherapy has reshaped relapsed B-ALL: the CD19xCD3 bispecific T-cell engager blinatumomab (TOWER) and the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (INO-VATE) both outperform salvage chemotherapy, and the CD19 CAR-T product tisagenlecleucel (ELIANA) produces high remission rates in paediatric and young-adult relapsed disease. For Ph+ ALL, BCR-ABL tyrosine kinase inhibitors, including the third-generation ponatinib, are integral. Allogeneic stem-cell transplant remains an option for high-risk or MRD-persistent patients. CNS prophylaxis is universal, reflecting ALL's propensity for meningeal involvement.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Blinatumomab (Blincyto) | 2014 (relapsed/refractory); later MRD+ and frontline consolidation | Relapsed/refractory and MRD-positive B-ALL | TOWER | Overall survival | Median OS ~7.7 vs 4.0 months vs chemotherapy (CD19xCD3 BiTE) |
| Inotuzumab ozogamicin (Besponsa) | 2017 | Relapsed/refractory B-ALL | INO-VATE | Complete remission rate / overall survival | CR/CRi ~81% vs ~29% with chemotherapy; higher MRD negativity |
| Tisagenlecleucel (Kymriah) | 2017 | Relapsed/refractory B-ALL up to age 25 | ELIANA | Overall remission rate | ORR ~81% within 3 months; durable remissions in paediatric/young-adult patients |
| Ponatinib (Iclusig) | 2012 (Ph+ leukaemias); 2024 frontline Ph+ ALL | Philadelphia-chromosome-positive ALL, including T315I | PACE; PhALLCON (frontline, with chemotherapy) | MRD-negative complete remission | PhALLCON showed superior MRD-negative CR vs imatinib in frontline Ph+ ALL |
| Imatinib (Gleevec) | Established for Ph+ ALL (with chemotherapy) | Frontline Philadelphia-chromosome-positive ALL | Cooperative-group chemotherapy-plus-TKI studies | Complete remission / survival | Markedly improved remission and transplant rates when added to chemotherapy in Ph+ ALL |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in acute lymphoblastic leukaemia (all) development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Rituximab (early anti-CD20 attempts in unselected ALL) — Various before CD20-selected use | Benefit was limited/inconsistent until restricted to CD20-positive B-ALL (later confirmed in GRAALL-2005) | Efficacy depends on CD20 antigen expression, so unselected use showed no clear advantage |
| Maxi/high-intensity chemotherapy escalation in older adults — Multiple older-adult intensification studies | Failed to improve survival because treatment-related toxicity offset any anti-leukaemic gain | Poor tolerance and comorbidity in older patients; helped drive the shift toward immunotherapy-based, lower-intensity approaches |
Choosing the right endpoint
Primary endpoints that matter in acute lymphoblastic leukaemia (all) trials
- Complete remission (CR/CRi) — Morphologic marrow clearance; foundational response measure
- Minimal residual disease (MRD) — Most powerful prognostic factor; MRD negativity guides transplant and therapy decisions
- Overall survival (OS) — Primary endpoint in relapsed adult trials such as TOWER
- Event-free survival (EFS) — Common in paediatric protocols capturing relapse and induction failure
- Overall/event-free remission rate — Key single-arm endpoint for CAR-T (ELIANA)
How iNGENū runs acute lymphoblastic leukaemia (all) trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Acute Lymphoblastic Leukaemia (ALL) clinical trials — FAQs
Why does ALL outcome differ so much between children and adults?
What is Philadelphia-chromosome-positive ALL?
How has immunotherapy changed relapsed B-ALL?
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