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MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted Methotrexate (LAL1913)

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ClinicalTrials.gov Identifier: NCT02067143
Recruitment Status : Completed
First Posted : February 20, 2014
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Tracking Information
First Submitted Date  ICMJE February 17, 2014
First Posted Date  ICMJE February 20, 2014
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE May 20, 2014
Actual Primary Completion Date October 7, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
Number of patients on disease free survival (DFS). [ Time Frame: At two years. ]
DFS is defined as the time interval between the evaluation of CR and relapse of the disease or death in first Complete Response (CR); patients still alive, in first CR, will be censored at the time of the last follow-up. In this case, the DFS will be truncated at 2 years.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
  • The rate of patients in complete remission (CR). [ Time Frame: After approximately two months from start of treatment. ]
  • The rate of early bone marrow MRD negativity. [ Time Frame: At 4 timepoints (week 4, 10, 16 22). ]
  • Early bone marrow MRD response (<10-4). [ Time Frame: At 4 weeks following induction cycle 1 with Peg-ASP. ]
  • Overall Survival (OS) estimation. [ Time Frame: At two years from diagnosis. ]
  • Cumulative Incidence of Relapse (CIR) estimation. [ Time Frame: At two years from CR achievement. ]
  • The rate of patients dead due Treatment-related mortality (TRM). [ Time Frame: By the end of the study (4.5 years from first centre opened). ]
  • Composite DFS, OS, CIR. [ Time Frame: At two years from CR achievement and rate of TRM in LL patients. ]
  • Description of Minimal Residual Disease (MRD) monitoring. [ Time Frame: During treatment at time point 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12. ]
  • Number of Severe Infections (SI) during treatment. [ Time Frame: At the end of the study (4.5 years from first centre opened). ]
    Description: Number and type.
  • Rate of Adverse Events (AE). [ Time Frame: By the end of the study (4.5 years from first centre opened) ]
    Excluding SI.
  • Composite evaluation of impact of age (≤55 and >55) and risk category group (SR, HR, VHR - as defined) on outcomes: DFS, CIR. [ Time Frame: At two years for CR achievement, OS at two years from diagnosis and TRM. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted Methotrexate
Official Title  ICMJE National Treatment Program of Philadelphia Chromosome-negative Adult Acute Lymphoblastic Leukemia With Pegylated Asparaginase Added to a Lineage-Targeted Risk- and Minimal Residual Disease-Oriented Strategy
Brief Summary This study will be conducted in different centres and will study adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). The study treatment will include a induction/consolidation therapy incorporating pegylated Asparaginase (Peg-ASP) and lineage-targeted high-dose methotrexate plus other antileukemic drugs, for the achievement of an early negative minimal residual disease (MRD) status. The MRD study supports a risk/MRD-oriented final consolidation phase.
Detailed Description The aim of this clinical study in adult ALL is to improve , by risk category, the overall disease-free survival in relation to the achievement of an early MRD negative status and following induction/consolidation with Peg-ASP, 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. A survey of severe infections occurring along the entire chemotherapy and stem cell transplant program and until 2 years from the achievement of CR will be performed with the aim to increase the knowledge of these complications and to evaluate their impact on the antileukemic program and on the long term outcome of the underlying malignancy. The prospective survey of severe infections will be performed as an ancillary observational objective of the present study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Untreated Philadelphia Positive Acute Lymphoblastic Leukemia
  • De Novo
  • Secondary
  • Low-dose Corticosteroids Pretreatment
Intervention  ICMJE
  • Drug: Prephase PDN + CY
  • Drug: Cycle 1 Induction
    Other Name: VCR + IDR + DXM + ASP + IT
  • Drug: Cycle 2 Induction / Early consolidation
    Other Name: IDR + CY + ARA-C + ASP + 6MP + DXM + IT
  • Drug: Cycle 3 Early consolidation
    Other Name: MTX + ARA-C
  • Drug: Cycle 4 Consolidation
    Other Name: VCR + IDR + CY + ARA-C + 6-MP + DXM + IT
  • Drug: Cycle 5 Consolidation
    Other Name: MTX + ASP + 6-MP
  • Drug: Cycle 6 Consolidation
    Other Name: VCR + IDR + CY + ARA-C + ASP + 6MP + DXM + IT
  • Drug: Cycle 7 Consolidation
    Other Name: MTX + ARA-C
  • Drug: Cycle 8 Reinduction
    Other Name: VCR + IDR + DXM + PDN + CY + IT
  • Drug: Maintenance
    If MRD negative MRD u/k SR
    Other Name: CY or VP and 6MP/MTX + 12 cycles of 6MP/MTX
  • Procedure: Allogeneic SCT or Autologous SCT
    If MRD positive MRD u/k HR
    Other Name: + Maintenance
Study Arms  ICMJE Experimental: Study population
In this phase II multicentric trial, eligible patients with Ph- ALL/LL will receive homogeneous supportive care and chemotherapy and will be homogeneously analyzed for response at prefixed timepoints from induction day 1. For risk-/MRD-oriented therapy, CR patients will be stratified by risk class according to diagnostic characteristics, MRD study and CT/PET (LL only) results during early consolidation.
Interventions:
  • Drug: Prephase PDN + CY
  • Drug: Cycle 1 Induction
  • Drug: Cycle 2 Induction / Early consolidation
  • Drug: Cycle 3 Early consolidation
  • Drug: Cycle 4 Consolidation
  • Drug: Cycle 5 Consolidation
  • Drug: Cycle 6 Consolidation
  • Drug: Cycle 7 Consolidation
  • Drug: Cycle 8 Reinduction
  • Drug: Maintenance
  • Procedure: Allogeneic SCT or Autologous SCT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2014)
204
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 7, 2020
Actual Primary Completion Date October 7, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed written informed consent according to ICH/EU/GCP and national local laws.
  • Age 18-65 years.
  • A diagnosis of untreated Ph- ALL or LL is required, either de novo or secondary to chemo-radiotherapy for other cancer. Pretreatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples. The diagnosis must be one of: de novo ALL, secondary ALL, B-/T-cell LL Full cytological, cytochemical, cytogenetic and immunobiological disease characterization according to EGIL and WHO classifications. Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) are required for MRD study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the forwarding of samples for MRD study are given in Appendix B.
  • Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) for MRD study.
  • ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself and not by preexisting comorbidity, and is considered and/or documented to be reversible following the application of antileukemic therapy and appropriate supportive measures.

Exclusion Criteria:

  • Diagnosis of Burkitt's leukemia or lymphoma.
  • Down's syndrome
  • Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, 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), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
  • Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is sent off study.
  • A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with life expectancy <1 year.
  • Pregnancy declared by the patient herself, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with ALL therapy. A pregnancy test is performed at diagnosis but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02067143
Other Study ID Numbers  ICMJE LAL1913
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gruppo Italiano Malattie EMatologiche dell'Adulto
Study Sponsor  ICMJE Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Renato Bassan, Pr. Azienda ULSS 12 Veneziana
Study Director: Roberto Foà, Pr. Policlinico Umberto I, Hematology Department.
PRS Account Gruppo Italiano Malattie EMatologiche dell'Adulto
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP