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Rituximab+mVPDL for CD20(+) Adult Acute Lymphoblastic Leukemia (RADICAL)

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ClinicalTrials.gov Identifier: NCT01429610
Recruitment Status : Unknown
Verified July 2018 by Je-Hwan Lee, Asan Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : September 7, 2011
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Je-Hwan Lee, Asan Medical Center

Tracking Information
First Submitted Date  ICMJE August 30, 2011
First Posted Date  ICMJE September 7, 2011
Last Update Posted Date July 24, 2018
Study Start Date  ICMJE November 2011
Actual Primary Completion Date January 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2011)
relapse-free survival (RFS) rate [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2011)
  • complete remission (CR) rates [ Time Frame: 4 weeks (from the initiation of induction treatment) ]
    among total patients / each subset of subsets A. [Subset A]
    1. Precursor B-cell vs. T-cell
    2. Younger (age<60 years) vs. older (age≥60 years)
    3. Risk group: standard vs. high
  • relapse-free survival rates [ Time Frame: 2 years ]
    among patients in each subset of A & B. [Subset A]
    1. Precursor B-cell vs. T-cell
    2. Younger (age<60 years) vs. older (age≥60 years)
    3. Risk group: standard vs. high. [Subset B]
    4. AlloHCT recipients vs. non-recipients.
  • overall survival rates [ Time Frame: 2 years ]
    among total patients / each subset of A & B [Subset A]
    1. Precursor B-cell vs. T-cell
    2. Younger (age<60 years) vs. older (age≥60 years)
    3. Risk group: standard vs. high [Subset B]
    4. AlloHCT recipients vs. non-recipients.
  • Cumulative incidence and maximal severity of acute / chronic graft-versus-host disease [ Time Frame: 2 years ]
    among alloHCT recipients
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 Rituximab+mVPDL for CD20(+) Adult Acute Lymphoblastic Leukemia
Official Title  ICMJE Phase 2 Study Evaluating the Efficacy of Rituximab Plus Modified VPDL for Newly Diagnosed CD20-Positive Adult Acute Lymphoblastic Leukemia
Brief Summary The investigators would like to propose a phase-2 prospective multicenter trial evaluating the efficacy of rituximab combination with our current chemotherapy strategy for adult Acute Lymphoblastic Leukemia (ALL), in order to prove out whether the addition of rituximab during induction, consolidation, and post-alloHCT status can improve the outcome in terms of relapse-free survival (RFS) when compared with our prior data as a historical control.
Detailed Description

According to the recent results on the outcome of escalated daunorubicin-based protocol for adult ALL which has been performed by 'Adult ALL Working Party of the Korean Society of Hematology' (data were announced at 2010 Annual Meeting of ASCO, Chicago, IL), CR rate of 90.6% was satisfactory, but the 2-year / 3-year disease-free survival (DFS) were disappointing (43.6% and 39.9%, respectively), which means that the adequate post-remission therapy to control minimal residual disease after the achievement of CR is very important to improve the outcome of adult ALL.

Allogeneic hematopoietic cell transplantation (AlloHCT) is recommended as a post-remission therapy for patients with adult ALL, and reduced intensity conditioning has been tried to decrease TRM rate. However, many patients received consolidation chemotherapy rather than alloHCT owing to the absence of HLA-matched donor, limitation of age, and combined comorbidities (among 190 patients who have been included in our previously-mentioned study, only 52.3% received alloHCT).

Recently, stagnation in the treatment of adult ALL appears to be reached, maybe due to a borderline for further intensification of chemotherapeutic dose. Dose-escalation strategy has many difficulties in adoption for the treatment of adult ALL in terms of increased morbidity and mortality, not to mention the efficacy of such strategies. New, preferably non-chemotherapy approaches (maybe targeted therapy) are therefore urgently required.

For Ph(+) ALL, the introduction of BCR/ABL tyrosine kinase inhibitor has improved the treatment outcome with tolerable toxicities. Applying a similar strategy to Ph(-) ALL, targeting leukemia surface antigens with monoclonal antibodies is another promising strategy.

CD 20 expression of at least 20% has been known to be found in 22-48% of pre-B ALL, and appears to be associated with a poor prognosis, although there are controversies in pediatric patients. Based on the significant improvement of the outcome in B-cell NHL, preliminary data regarding the use of rituximab in frontline therapy for CD20-positive precursor B-cell ALL suggest its use may be beneficial. Especially, monoclonal antibodies are thought to be more effective when combined with chemotherapy and treated in the state of minimal residual disease, which suggests the interest of evaluating rituximab combined to current chemotherapy of adult ALL. Recent data on the efficacy of rituximab-combined chemotherapy showed that rates of CR and OS were superior with the modified hyperCVAD and rituximab regimens compared with standard hyper-CVAD (70% versus 38%, p<0.001) in younger (age < 60 years) CD20-positive subset, although it was an analysis of different patient groups who were treated with various regimen5.

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 Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention  ICMJE Drug: Rituximab+mVPDL
  1. Induction:

    • Dauno 90 mg/m2/d by civ (d1-3)
    • Vinc 2 mg iv (d1, 8)
    • Pred 60 mg/m2/d po (d1-14)
    • for Ph(-): L-asp 4,000 units/m2/day im/sc (d17-28) for Ph(+): Imatinib 600mg/d po qd (d8-continue till the end of maintenance or just before alloHCT)
    • Rituximab 375mg/m2/d (d8)
  2. Consolidation A (cycle1)

    • D 45 mg/m2/day by continuous iv (d1, 2)
    • V 2 mg iv (d1, 8)
    • P 60 mg/m2/day po (d1-14)
    • for Ph(-): L-asp (d1-14) for Ph(+): Imatinib
    • Rituximab 375mg/m2/d (d8)
  3. Consolidation B (cycles2&4)

    • Cyt 2,000 mg/m2/d iv over 2 hr (d1-4)
    • Eto 150 mg/m2/d iv over 3 hr (d1-4)
    • Rituximab 375mg/m2/d d8
  4. Consolidation C (cycles 3&5)

    • Methotrexate 220 mg/m2 iv bolus, then 60mg/m2/h for 36 hr (d1-2, 15-16)
    • Leucovorin 50 mg/m2 iv every 6hr for 3 doses,
    • Rituximab 375mg/m2/d (d8&22)
  5. Maintenance (for 2 years)

    - for Ph(-): 6- Mercaptopurine 60 mg/m2 po qd Methotrexate 20 mg/m2 po qw for Ph(+): imatinib 600mg/d po qd

  6. Consider alloHCT
Other Names:
  • Mabthera
  • VCS
  • Daunobrastina
  • Solondo
  • Leunase
  • Cytarabine
  • Efosin
  • DBLMethotrexate
Study Arms  ICMJE Experimental: Rituximab+mVPDL
Patients who were CD20(+), newly-diagnosed adult ALL and treated with rituximab + mVPDL treatment plan
Intervention: Drug: Rituximab+mVPDL
Publications *

*   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 Unknown status
Actual Enrollment  ICMJE
 (submitted: July 18, 2017)
78
Original Estimated Enrollment  ICMJE
 (submitted: September 3, 2011)
77
Estimated Study Completion Date  ICMJE January 1, 2019
Actual Primary Completion Date January 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients who were previously untreated and had either ALL or high-risk lymphoblastic lymphoma.
  • Patients whose leukemic blast cells express ≥20% of CD20 antigens at time of diagnosis
  • No prior chemotherapy for leukemia (use of hydroxyurea or leukapheresis are permitted.)
  • Estimated life expectancy of more than 3 months
  • ECOG performance status of 2 or lower, Karnofsky scale > 60
  • Adequate cardiac function (EF>45%) on echocardiogram or Heart scan (MUGA scan)
  • 15 years of age and over.
  • Adequate renal function (creatinine<1.5 mg/dL)
  • Adequate hepatic function. (Bilirubin<1.5 mg/dL, transaminases levels<3 times the upper normal limit [5 times for patients with liver metastasis or hepatomegaly]). Even the initial level exceed the upper limits, patient will be acceptable when the levels on day 8 satisfies the inclusion criteria.
  • All patients gave written informed consent according to guidelines at each institution's committee on human research.

Exclusion Criteria:

  • Acute biphenotypic leukemia, acute biclonal leukemia, or acute mixed leukemia
  • Presence of significant uncontrolled active infection
  • Presence of uncontrolled bleeding
  • Any coexisting major illness or organ failure
  • Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
  • Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
  • Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, 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 Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01429610
Other Study ID Numbers  ICMJE KALLA0804
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Je-Hwan Lee, Asan Medical Center
Study Sponsor  ICMJE Asan Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Young Don Joo, MD, PhD Inje University
PRS Account Asan Medical Center
Verification Date July 2018

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