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

NCT00795756 | Completed Phase 2 DMC

• 1 other identifier: NILG-ALL 10/07
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 16

Brief 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 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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Adults; Central nervous system prophylaxis; Minimal residual disease

Outcome Measures

Primary Outcomes (1)

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

  weeks 5, 11, 17 and 23

Secondary Outcomes (5)

• Comparative analysis of isolated and combined CNS recurrence following TIT vs DepoCyte prophylaxis

  During study follow-up

• Complete remission (CR)

  After study chemotherapy cycles 1 and 2

• Bone marrow MRD negativity rates

  Four time-points at weeks 4-22

• Lenght of remission

  Study follow-up

• Overall survival

  Study follow-up

Study Arms (2)

Intrathecal DepoCyte

EXPERIMENTAL

I.t. DepoCyte 50 mg admninistered x6-8 (depending on immunophenotypic disease subset) during induction/consolidation/eraly maintenance phases

Drug: liposome-encapsulated cytarabine (DepoCyte)

Triple intrathecal therapy (TIT)

ACTIVE COMPARATOR

Methotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg injected intrathecally x12 during indiction/consolidation phases

Drug: Triple intrathecal therapy (TIT)

Interventions

liposome-encapsulated cytarabine (DepoCyte) DRUG

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

Also known as: DepoCyte, DepoCyt

Intrathecal DepoCyte

Triple intrathecal therapy (TIT) DRUG

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

Also known as: Methotrexate, Cytosine arabinoside, Cytosar

Triple intrathecal therapy (TIT)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northern Italy Leukemia Group: lead

Study Sites (16)

USC Ematologia, Ospedale Civile

Alessandria, (al), Italy

Location

USC Ematologia, Ospedali Riuniti

Bergamo, (bg), 24128, Italy

Location

Divisione di Ematologia - Spedali Civili

Brescia, (bs), Italy

Location

Divisione di Ematologia e TMO, Ospedale San Maurizio

Bolzano, (bz), Italy

Location

Ematologia e centro TMO - Ospedale Armando Businco

Cagliari, (ca), Italy

Location

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

Cuneo, (cn), Italy

Location

Ematologia e centro TMO, Istituti Ospedalieri

Cremona, (cr), Italy

Location

Ematologia - AOU Careggi

Florence, (fi), Italy

Location

Ematologia e centro TMO - IRCSS Mangiagalli Regina Elena

Milan, (mi), Italy

Location

Ematologia e centro TMO, Ospedale San Raffaele

Milan, (mi), Italy

Location

Ematologia e centro TMO, Ospedale San Gerardo

Monza, (mi), Italy

Location

Oncoematologia e TMO - Dipartimento Oncologico La Maddalena

Palermo, (pa), Italy

Location

Ematologia 2 - Ospedale San Giovanni Battista

Torino, (to), Italy

Location

Medicina Interna I - Ospedale di Circolo

Varese, (va), Italy

Location

Onco-Ematologia - Ospedale Civile

Noale, (ve), Italy

Location

Ematologia - Ospedale San Bortolo

Vicenza, (vi), Italy

Location

Related Publications (1)

• 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.

  PMID: 25749825 DERIVED

Related Links

• Web site of NILG-ALL 10/07 protocol. Accessible to study participants only.

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

Methotrexate; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Renato Bassan, MD

  USC Ematologia, Ospedali Riuniti, Bergamo (Italy)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: November 19, 2008
• First Posted: November 21, 2008
• Study Start: January 1, 2008
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 22, 2014

Record last verified: 2014-10

Locations

IT (16)