Know Cancer

forgot password

A Randomized Study on CNS Prophylaxis With Liposome-Encapsulated Cytarabine in Association With a Lineage-Targeted and MRD-Oriented Postremission Strategy in Adult ALL

Phase 2/Phase 3
18 Years
65 Years
Open (Enrolling)
Acute Lymphoblastic Leukemia

Thank you

Trial Information

A Randomized Study on CNS Prophylaxis With Liposome-Encapsulated Cytarabine in Association With a Lineage-Targeted and MRD-Oriented Postremission Strategy in Adult ALL

A) Risk Classification

Newly diagnosed patients are hierarchically clustered into very high, high and standard risk
cases (VHR, HR, SR) using international risk criteria modified according to NILG:

A1) VHR (any criterium): B-precursor: WBC count >100x109/L; adverse cytogenetics/molecular
biology such as t(9;22)/BCR-ABL, t(4;11)/MLL rearrangement at 11q23, +8, -7, del6q, t(8;14),
low hypodiploidy with 30-39 chromosomes, near triploidy with 60-78 chromosomes, complex with
>5 unrelated anomalies. T-precursor: WBC count >100x109/L; early/late non-cortical
immunophenotype (CD1a-); adverse cytogenetics/molecular biology (as above).

A2) HR (any criterium, VHR excluded): B-precursor: WBC count >30x109/L; pro-B
immunophenotype; complete remission after cycle 2. T-precursor: complete remission after
cycle 2.

A3) SR (all criteria, VHR/HR excluded): B-precursor: WBC count <30x109/L; T-precursor: WBC
count <100x109/L; cortical immunophenotype (CD1a+).

B) CNS Prophylaxis Stratification before randomisation

1. by immunophenotype, i.e. B-precursor vs. T-precursor

2. by risk class, i.e. SR vs. non-SR (using only known factors) Randomisation: intrathecal
(IT) CNS prophylaxis with standard triple therapy (TIT, 12 total injections) vs.
DepoCyte (6-8 total injections by disease subset). Cranial irradiation is omitted in
both arms, and all patients receive the same chemotherapy program including
CNS-crossing agents.

C)Induction/Early Consolidation and MRD Study

Randomised patients receive homogeneous induction/early consolidation chemotherapy,
including subset-specific elements for B-precursor ALL (3x targeted-infusion methotrexate
2.5 g/m2), T-precursor ALL (3x targeted-infusion methotrexate 5 g/m2), age >55 years
(methotrexate reduced to 1.5 g/m2), Ph/BCR-ABL+ ALL (imatinib, reduced-intensity
chemotherapy), radiation therapy (LL). Patients not in CR after cycles 1-2 are off study.
For CR evaluation bone marrow is checked on days 28 and/or 56. Consolidation cycles are
administered at 21-28 day intervals Concurrent MRD analysis is performed at four timepoints
(weeks 4, 10, 16 and 22 of induction/consolidation), to optimize risk classification and
support risk/MRD-oriented therapy:

C1) MRD negative (M-NEG): negative MRD study (<10-4 at timepoints #2 and #3, and negative at
timepoint #4) C2) MRD positive (M-POS): positive MRD study (>10-4 at timepoints #2 or #3, or
positive at timepoint #4)

D)MRD/Risk-Oriented Final Therapy D1) VHR patients are candidate to an early allogeneic SCT
(related/unrelated donor/cord blood; ablative/non-ablative conditioning according to current
protocols/guidelines) after CR, regardless MRD study results.

D2) M-POS as well as HR patients with unknown MRD are allocated to allogeneic SCT after MRD
timepoint 2 (M-POS >10-4) or MRD timepoint 4 (others). When an allogeneic SCT is not
possible, patients complete consolidation and receive autologous-type SCT followed by

D3) M-NEG as well as SR patients with unknown MRD are allocated to maintenance therapy.

Age-limited therapeutic procedures: Patients aged >55 years are treated with age-adapted
therapy, and when indicated will be included in SCT programs whenever possible and according
to performance status and comorbidity.

Inclusion Criteria:

- Age 18-65 years.

- Diagnosis of untreated ALL with B-/T-precursor phenotype or B-cell lymphoblastic
lymphoma (B-LL), either de novo or secondary to chemo-radiotherapy for other cancer.

- Full cytological, cytochemical, cytogenetic and immunobiological disease
characterization by revised FAB, EGIL and WHO criteria.

- Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) for MRD

- ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of

- Signed informed consent.

Exclusion Criteria:

- Diagnosis of B-ALL (FAB L3 ALL/Burkitt's leukemia or lymphoma) and T-LL (T-cell
lymphoblastic lymphoma).

- Down's syndrome.

- Pre-existing, uncontrolled pathology such as cardiac disease (congestive/ischemic,
acute myocardial infarction within the past 3 months, untreatable arrythmias, NYHA
classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3
x upper normal limit (unless attributable to ALL/LL), kidney function impairment with
serum creatinine >2 mg/dL (unless attributable to ALL/LL), and severe neurological or
psychiatric disorder that impairs the patient's ability to understand and sign the
informed consent, or to cope with the intended treatment plan.

- Known HIV positive serology.

- Other active hematological or non-hematological cancer with life expectancy <1 year.

- Pregnancy (fertile women will be advised not to become pregnant while on treatment;
and male patients to adopt contraceptive methods), unless therapeutic aborption/early
discharge is carried out.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparative analysis of feasibility/toxicity of IT DepoCyte vs. TIT

Outcome Time Frame:

weeks 5, 11, 17 and 23

Safety Issue:


Principal Investigator

Renato Bassan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

USC Ematologia, Ospedali Riuniti, Bergamo (Italy)


Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Study ID:

NILG-ALL 10/07



Start Date:

January 2008

Completion Date:

December 2012

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Adults
  • Central nervous system prophylaxis
  • Minimal residual disease
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Neoplasm, Residual