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Acute Lymphoblastic LeukemiaPhase 2/3NCT00795756

Intrathecal DepoCyte and Lineage-targeted Minimal Residual Disease-oriented Therapy of Acute Lymphoblastic Leukemia

A Phase 2/3 study testing liposome-encapsulated cytarabine (DepoCyte) and Triple intrathecal therapy (TIT) in people with Acute Lymphoblastic Leukemia, run by Northern Italy Leukemia Group at 16 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this clinical study in adult ALL is to compare by risk category (1) the feasibility of two different CNS prophylaxis regimens and (2) the overall disease-free survival in relation to the achievement of an early MRD negative status and following consolidation with lineage-targeted methotrexate infusions and… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
liposome-encapsulated cytarabine (DepoCyte) and Triple intrathecal therapy (TIT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
16 sitesItaly
Study dates
Jan 2008to Oct 2013
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 study.
  • ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of complications.
  • Signed informed consent.

Who cannot join

  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Italy16 sites
  • USC Ematologia, Ospedale Civile

    Alessandria, (al)

  • USC Ematologia, Ospedali Riuniti

    Bergamo, (bg), 24128

  • Divisione di Ematologia e TMO, Ospedale San Maurizio

    Bolzano, (bz)

  • Divisione di Ematologia - Spedali Civili

    Brescia, (bs)

  • Ematologia e centro TMO - Ospedale Armando Businco

    Cagliari, (ca)

  • Ematologia e centro TMO, Istituti Ospedalieri

    Cremona, (cr)

  • S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

    Cuneo, (cn)

  • Ematologia - AOU Careggi

    Florence, (fi)

  • Ematologia e centro TMO - IRCSS Mangiagalli Regina Elena

    Milan, (mi)

  • Ematologia e centro TMO, Ospedale San Raffaele

    Milan, (mi)

  • Ematologia e centro TMO, Ospedale San Gerardo

    Monza, (mi)

  • Onco-Ematologia - Ospedale Civile

    Noale, (ve)

  • Oncoematologia e TMO - Dipartimento Oncologico La Maddalena

    Palermo, (pa)

  • Ematologia 2 - Ospedale San Giovanni Battista

    Torino, (to)

  • Medicina Interna I - Ospedale di Circolo

    Varese, (va)

  • Ematologia - Ospedale San Bortolo

    Vicenza, (vi)

Other trials in Italy

About this study

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

The aim of this clinical study in adult ALL is to compare by risk category (1) the feasibility of two different CNS prophylaxis regimens and (2) the overall disease-free survival in relation to the achievement of an early MRD negative status and following consolidation with lineage-targeted methotrexate infusions and other disease-specific therapeutic elements, with or without the application of allogeneic or autologous SCT depending on risk class and MRD study results.

In this multicentric prospective pilot randomized phase II trial on CNS prophylaxis, all patients receive induction/consolidation therapy incorporating lineage-targeted high-dose methotrexate plus other drugs (with additional imatinib in Ph/BCR-ABL+ ALL), for the achievement of an early negative MRD status. The MRD study supports a risk/MRD-oriented final consolidation phase.

Read the detailed description
  1. 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+).

  1. CNS Prophylaxis Stratification before randomisation
  2. by immunophenotype, i.e. B-precursor vs. T-precursor
  3. 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 maintenance.

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.

Being tested
liposome-encapsulated cytarabine (DepoCyte), Triple intrathecal therapy (TIT)
Keywords
Adults, Central nervous system prophylaxis, Minimal residual disease
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • liposome-encapsulated cytarabine (DepoCyte)Drug

    Also called DepoCyte, DepoCyt

    DepoCyte 50 mg injected intrathecally x6-8 (6: B-lineage, 8: T-lineage) during induction/consolidation phases

  • Triple intrathecal therapy (TIT)Drug

    Also called Methotrexate, Cytosine arabinoside, Cytosar

    Methotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg. injected intrathecally x12 during induction/consolidation therapy

Study groups in NCT00795756
Study groupRoleWhat they receive
Intrathecal DepoCyteExperimentalI.t. DepoCyte 50 mg admninistered x6-8 (depending on immunophenotypic disease subset) during induction/consolidation/eraly maintenance phases
Receives: Drug: liposome-encapsulated cytarabine (DepoCyte)
Triple intrathecal therapy (TIT)Active comparatorMethotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg injected intrathecally x12 during indiction/consolidation phases
Receives: Drug: Triple intrathecal therapy (TIT)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: weeks 5, 11, 17 and 23

Secondary outcomes (5)
  1. Comparative analysis of isolated and combined CNS recurrence following TIT vs DepoCyte prophylaxis

    Measured: During study follow-up

  2. Complete remission (CR)

    Measured: After study chemotherapy cycles 1 and 2

  3. Bone marrow MRD negativity rates

    Measured: Four time-points at weeks 4-22

  4. Lenght of remission

    Measured: Study follow-up

  5. Overall survival

    Measured: Study follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00795756
Sponsor's protocol ID
NILG-ALL 10/07
Status last verified
Oct 2014
First submitted
19 Nov 2008
Last updated
22 Oct 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Bassan R, Masciulli A, Intermesoli T, Audisio E, Rossi G, Pogliani EM, Cassibba V, Mattei D, Romani C, Cortelezzi A, Corti C, Scattolin AM, Spinelli O, Tosi M, Parolini M, Marmont F, Borlenghi E, Fumagalli M, Cortelazzo S, Gallamini A, Marfisi RM, Oldani E, Rambaldi A. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia. Haematologica. 2015 Jun;100(6):786-93. doi: 10.3324/haematol.2014.123273. Epub 2015 Mar 6.

    PubMed 25749825

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing liposome-encapsulated cytarabine (DepoCyte) and Triple intrathecal therapy (TIT) in people with Acute Lymphoblastic Leukemia, run by Northern Italy Leukemia Group at 16 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparative analysis of feasibility/toxicity of IT DepoCyte vs. TIT (time frame: weeks 5, 11, 17 and 23). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00795756, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2014.

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