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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
DR RENATO BASSAN, Northern Italy Leukemia Group
ClinicalTrials.gov Identifier:
NCT00795756
First received: November 19, 2008
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: liposome-encapsulated cytarabine (DepoCyte)
Drug: Triple intrathecal therapy (TIT)
Phase 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Northern Italy Leukemia Group:

Primary Outcome Measures:
  • Comparative analysis of feasibility/toxicity of IT DepoCyte vs. TIT [ Time Frame: weeks 5, 11, 17 and 23 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparative analysis of isolated and combined CNS recurrence following TIT vs DepoCyte prophylaxis [ Time Frame: During study follow-up ] [ Designated as safety issue: No ]
  • Complete remission (CR) [ Time Frame: After study chemotherapy cycles 1 and 2 ] [ Designated as safety issue: No ]
  • Bone marrow MRD negativity rates [ Time Frame: Four time-points at weeks 4-22 ] [ Designated as safety issue: No ]
  • Lenght of remission [ Time Frame: Study follow-up ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Study follow-up ] [ Designated as safety issue: No ]

Enrollment: 145
Study Start Date: January 2008
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrathecal DepoCyte
I.t. DepoCyte 50 mg admninistered x6-8 (depending on immunophenotypic disease subset) during induction/consolidation/eraly maintenance phases
Drug: liposome-encapsulated cytarabine (DepoCyte)
DepoCyte 50 mg injected intrathecally x6-8 (6: B-lineage, 8: T-lineage) during induction/consolidation phases
Other Names:
  • DepoCyte
  • DepoCyt
Active Comparator: Triple intrathecal therapy (TIT)
Methotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg injected intrathecally x12 during indiction/consolidation phases
Drug: Triple intrathecal therapy (TIT)
Methotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg. injected intrathecally x12 during induction/consolidation therapy
Other Names:
  • Methotrexate
  • Cytosine arabinoside
  • Cytosar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 study.
  • ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of complications.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00795756

Locations
Italy
USC Ematologia, Ospedale Civile
Alessandria, (al), Italy
USC Ematologia, Ospedali Riuniti
Bergamo, (bg), Italy, 24128
Divisione di Ematologia - Spedali Civili
Brescia, (bs), Italy
Divisione di Ematologia e TMO, Ospedale San Maurizio
Bolzano, (bz), Italy
Ematologia e centro TMO - Ospedale Armando Businco
Cagliari, (ca), Italy
S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
Cuneo, (cn), Italy
Ematologia e centro TMO, Istituti Ospedalieri
Cremona, (cr), Italy
Ematologia - AOU Careggi
Firenze, (fi), Italy
Ematologia e centro TMO - IRCSS Mangiagalli Regina Elena
Milano, (mi), Italy
Ematologia e centro TMO, Ospedale San Raffaele
Milano, (mi), Italy
Ematologia e centro TMO, Ospedale San Gerardo
Monza, (mi), Italy
Oncoematologia e TMO - Dipartimento Oncologico La Maddalena
Palermo, (pa), Italy
Ematologia 2 - Ospedale San Giovanni Battista
Torino, (to), Italy
Medicina Interna I - Ospedale di Circolo
Varese, (va), Italy
Onco-Ematologia - Ospedale Civile
Noale, (ve), Italy
Ematologia - Ospedale San Bortolo
Vicenza, (vi), Italy
Sponsors and Collaborators
Northern Italy Leukemia Group
Investigators
Study Chair: Renato Bassan, MD USC Ematologia, Ospedali Riuniti, Bergamo (Italy)
  More Information

No publications provided

Responsible Party: DR RENATO BASSAN, Medical Doctor, Northern Italy Leukemia Group
ClinicalTrials.gov Identifier: NCT00795756     History of Changes
Other Study ID Numbers: NILG-ALL 10/07
Study First Received: November 19, 2008
Last Updated: October 21, 2014
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Northern Italy Leukemia Group:
Adults
Central nervous system prophylaxis
Minimal residual disease

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Cytarabine
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014