A Study for Older Adults With Acute Lymphoblastic Leukaemia

Study Overview
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Brief Summary
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The NCRI Adult ALL sub-group propose to collaborate with the Dutch/Belgian group HOVON to carry out a prospective, non randomised multi-arm study (including a choice of regimen intensity) to investigate the safety, tolerability and feasibility of a standardised therapy protocol for patients ≥ 60 years old with de novo ALL. The overall aim is define a basic standard of care upon which trials of novel therapies will be based in future. The design of the study will enable collection of a comprehensive dataset regarding the clinical outcome, Complete Response Rate (CR) and Minimal Residual Disease (MRD) response rates in a previously completely uncharacterised population, thus providing the essential platform for designing future randomised advanced phase studies in which new therapeutic approaches and novel therapies can be prospectively investigated.

Detailed Description
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The study will establish baseline expectations for Event Free Survival (EFS), Overall Survival (OS), MRD responses and quality of life measures for older patients of all ages and pre-morbid states; disclose how best to use knowledge of pre-morbid characteristics to apply the appropriate intensity of therapy in order to balance the best disease related outcomes against quality of life; establish national standards of care for this patient group; provide the essential platform for careful design of future randomised advanced phase studies of new therapeutic approaches and agents.

Official Title
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A Phase 2 Study for Older Adults With Acute Lymphoblastic Leukaemia

Conditions
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Acute Lymphoblastic Leukaemia

Intervention / Treatment
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* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 60 with Acute Lymphoblastic Leukaemia (ALL) OR ≥ 55 with Acute Lymphoblastic Leukaemia (ALL) unsuitable for the UKALL14 or HOVON 100 trial Newly diagnosed, previously untreated ALL (a steroid pre-phase of 5-7 days may be given before trial registration)) Willing and able to give consent Exclusion Criteria: Known HIV infection Blast transformation of CML Mature B-cell leukaemia i.e. Burkitts disease t(8,14)(q24 ;q32) and variant c-myc translocations e.g. t(2;8)(p12 ;q24), t(8;22)(q24;q11) Women who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Philadelphia Positive Patients<br>All patients with Philadelphia positive ALL will be treated in this group and will receive a standard imatinib-containing chemotherapy regimen | Drug: Chemotherapy<br>* Treatment for all pathways consists of Induction, Intensification (where applicable), Consolidation and Maintenance therapy during which combination chemotherapy is given for up to 2.5 years.<br>|
| Experimental: Philadelphia -ve Patients- Intensive<br>Patients with Philadelphia negative ALL who are fit for intensive treatment will be allocated into this group. | Drug: Chemotherapy<br>* Treatment for all pathways consists of Induction, Intensification (where applicable), Consolidation and Maintenance therapy during which combination chemotherapy is given for up to 2.5 years.<br>|
| Experimental: Philadelphia -ve Patients- Intensive +<br>Patients with Philadelphia negative disease and who are fit for intensive treatment will be entered into this group | Drug: Chemotherapy<br>* Treatment for all pathways consists of Induction, Intensification (where applicable), Consolidation and Maintenance therapy during which combination chemotherapy is given for up to 2.5 years.<br>|
| Experimental: Philadelphia -ve Patients- Non Intensive<br>Patients with Philadelphia negative disease who are not fit for intensive chemotherapy will be entered into this group | Drug: Chemotherapy<br>* Treatment for all pathways consists of Induction, Intensification (where applicable), Consolidation and Maintenance therapy during which combination chemotherapy is given for up to 2.5 years.<br>|
| No Intervention: Registration only<br>Patients with either Philadelphia positive or negative ALL who do not wish to enter the study will be allocated to this group for data collection purposes only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate after 2 phases of induction | All patients will be assessed for their remission status at the end of Phase 2 induction. The CR rate at this timepoint will then be calculated. | Approximately 2 months after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate after 1 phase of induction | All patients will be assessed for their remission status at the end of Phase 1 induction. The CR rate at this timepoint will then be calculated. | Approximately 1 month after start of treatment | 
| Overall Survival at 1 year | Overall survival for all patients will be measured 1 year after registration | 1 year after registration | 
| Prognostic significance of molecularly determined minimal residual disease (MRD) at various time-points during therapy with respect to relapse occurrence. | MRD levels will be measured at distinct timepoints during the trial. | At diagnosis, 4 weeks, 8 weeks, 12 weeks after starting treatment | 
| Tolerability of treatment as determined by occurrence of key adverse effects | Patients in arms A-D will be assessed for adverse events at distinct timepoints during the trial | Approximately 4 weeks, 8 weeks, 12 weeks, 24 weeks after starting treatment | 
| Duration of in-patient hospitalisation | All patients will be assessed for the number of days they have spent as in-patients at distinct timepoints during the trial. | Approximately 4 weeks, 8 weeks, 12 weeks, 24 weeks, 28 after starting treatment and every 3 months during maintenance | 
| Relationship between performance status/co-morbidity and treatment option chosen |  | At registration | 
| Quality of life aspects assessed at diagnosis/baseline at various time points |  | Registration, Approximately 4 weeks, 8 weeks, 12 weeks, 24 weeks, 28 after starting treatment, before starting maintenance and at the end of maintenance |