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

Sponsor
Asan Medical Center (Other)
Overall Status
Unknown status
CT.gov ID
NCT01429610
Collaborator
(none)
78
Enrollment
19
Locations
1
Arm
86
Duration (Months)
4.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
78 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2 Study Evaluating the Efficacy of Rituximab Plus Modified VPDL for Newly Diagnosed CD20-Positive Adult Acute Lymphoblastic Leukemia
Study Start Date :
Nov 1, 2011
Actual Primary Completion Date :
Jan 1, 2018
Anticipated Study Completion Date :
Jan 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rituximab+mVPDL

Patients who were CD20(+), newly-diagnosed adult ALL and treated with rituximab + mVPDL treatment plan

Drug: Rituximab+mVPDL
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) 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) 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 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) 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 Consider alloHCT
Other Names:
  • Mabthera
  • VCS
  • Daunobrastina
  • Solondo
  • Leunase
  • Cytarabine
  • Efosin
  • DBLMethotrexate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. relapse-free survival (RFS) rate [2 years]

    Secondary Outcome Measures

    1. complete remission (CR) rates [4 weeks (from the initiation of induction treatment)]

      among total patients / each subset of subsets A. [Subset A] Precursor B-cell vs. T-cell Younger (age<60 years) vs. older (age≥60 years) Risk group: standard vs. high

    2. relapse-free survival rates [2 years]

      among patients in each subset of A & B. [Subset A] Precursor B-cell vs. T-cell Younger (age<60 years) vs. older (age≥60 years) Risk group: standard vs. high. [Subset B] AlloHCT recipients vs. non-recipients.

    3. overall survival rates [2 years]

      among total patients / each subset of A & B [Subset A] Precursor B-cell vs. T-cell Younger (age<60 years) vs. older (age≥60 years) Risk group: standard vs. high [Subset B] AlloHCT recipients vs. non-recipients.

    4. Cumulative incidence and maximal severity of acute / chronic graft-versus-host disease [2 years]

      among alloHCT recipients

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chonnam National University Hwasun Hospital Hwasun Chollanamdo Korea, Republic of
    2 Hematologic Oncology Clinic, National Cancer Center Ilsan Kongki Korea, Republic of
    3 Division of Hematology-Oncology, Dong-A University College of Medicine Busan Korea, Republic of
    4 Dong-A University College of Medicine Busan Korea, Republic of
    5 Inje University Busan Paik Hospital Busan Korea, Republic of
    6 Inje University Haeundae-Paik Hospital Busan Korea, Republic of
    7 Kosin University College of Medicine, Kosin University Gospel Hospital Busan Korea, Republic of
    8 Catholic University of Daegu School of Medicine Daegu Korea, Republic of
    9 Keimyung University Dongsan Medical Center Daegu Korea, Republic of
    10 Kyungpook National Unviersity Hospital Daegu Korea, Republic of
    11 Yeungnam University College of Medicine Daegu Korea, Republic of
    12 Chungnam National University Hospital Daejeon Korea, Republic of
    13 Asan Medical Center, University of Ulsan College of Medicine Seoul Korea, Republic of
    14 Chung-Ang University Hospital Seoul Korea, Republic of
    15 Ewha Womans University Mokdong Hospital Seoul Korea, Republic of
    16 Korea University Anam Hospital Seoul Korea, Republic of
    17 Seoul National University Hospital Seoul Korea, Republic of
    18 Soonchunhyang University Hospital Seoul Korea, Republic of
    19 Ulsan University Hospital, University of Ulsan College of Medicine Ulsan Korea, Republic of

    Sponsors and Collaborators

    • Asan Medical Center

    Investigators

    • Principal Investigator: Young Don Joo, MD, PhD, Inje University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Je-Hwan Lee, Professor, Asan Medical Center
    ClinicalTrials.gov Identifier:
    NCT01429610
    Other Study ID Numbers:
    • KALLA0804
    First Posted:
    Sep 7, 2011
    Last Update Posted:
    Jul 24, 2018
    Last Verified:
    Jul 1, 2018
    Keywords provided by Je-Hwan Lee, Professor, Asan Medical Center
    acute lymphoblastic leukemia
    rituximab
    VPDL
    CD20
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Cytarabine
    Rituximab

    Study Results

    No Results Posted as of Jul 24, 2018