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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Asan Medical Center
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
First received: August 30, 2011
Last updated: July 1, 2015
Last verified: July 2015
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 Intervention Phase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug: Rituximab+mVPDL
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • relapse-free survival (RFS) rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • complete remission (CR) rates [ Time Frame: 4 weeks (from the initiation of induction treatment) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    among alloHCT recipients

Estimated Enrollment: 77
Study Start Date: November 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab+mVPDL
Patients who were CD20(+), newly-diagnosed adult ALL and treated with rituximab + mVPDL treatment plan
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

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.


Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
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
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: NCT01429610

Contact: Dae-Young Kim, MD, PhD 82-2-3010-5930 dani@amc.seoul.kr
Contact: Ji Eun Park, RN 82-2-3010-8261 je3.park@gmail.com

Korea, Republic of
Chonnam National University Hwasun Hospital Recruiting
Hwasun, Chollanamdo, Korea, Republic of
Contact: Lee       kaosin@naver.com   
Sub-Investigator: Jae-Sook Ahn, MD         
Sub-Investigator: Je-Jung Lee, MD, PhD         
Sub-Investigator: Sung-Hoon Jung, MD         
Principal Investigator: Deok-Hwan Yang, MD, PhD         
Hematologic Oncology Clinic, National Cancer Center Recruiting
Koyang, Kongki, Korea, Republic of
Contact: Yoon       taikoo2@ncc.re.kr   
Principal Investigator: Hyeon Seok Eom, MD, PhD         
Sub-Investigator: Hyewon Lee, MD         
Gyeonsang National University Hospital Gyeongsang National University School of Medicine Withdrawn
Jinju, Kyongsangnam-do, Korea, Republic of
Division of Hematology-Oncology, Dong-A University College of Medicine Recruiting
Busan, Korea, Republic of
Contact: Lee    82-51-240-5044    br2916@hanmail.net   
Principal Investigator: Sung-Hyun Kim, MD, PhD         
Dong-A University College of Medicine Recruiting
Busan, Korea, Republic of
Contact: Lee       br2916@hanmail.net   
Principal Investigator: Sung-Hyun Kim, MD, PhD         
Inje University Busan Paik Hospital Recruiting
Busan, Korea, Republic of
Contact: Moon       irein2000@nate.com   
Principal Investigator: Won Sik Lee, MD, PhD         
Sub-Investigator: Sang Min Lee, MD, PhD         
Inje University Haeundae-Paik Hospital Recruiting
Busan, Korea, Republic of
Contact: Kwon       rainbow325@nate.com   
Principal Investigator: Young Don Joo, MD, PhD         
Kosin University College of Medicine, Kosin University Gospel Hospital Recruiting
Busan, Korea, Republic of
Contact: Lim       poya1949@paran.com   
Principal Investigator: Yang Soo Kim, MD, PhD         
Sub-Investigator: Ho-Sup Lee, MD, PhD         
Chungbuk National University Hospital Withdrawn
Cheongju, Korea, Republic of
Catholic University of Daegu School of Medicine Recruiting
Daegu, Korea, Republic of
Contact: Shin       EunjiShin@paran.com   
Principal Investigator: Sung Hwa Bae, MD, PhD         
Sub-Investigator: Hun Mo Ryoo, MD, PhD         
Keimyung University Dongsan Medical Center Recruiting
Daegu, Korea, Republic of
Contact: Park       socool6014@naver.com   
Principal Investigator: Young Rok Do, MD, PhD         
Sub-Investigator: Ki Young Kwon, MD, PhD         
Sub-Investigator: Jin Young Kim, MD         
Kyungpook National Unviersity Hospital Recruiting
Daegu, Korea, Republic of
Contact: Choi       aimerchi@naver.com   
Principal Investigator: Sang Kyun Sohn, MD, PhD         
Sub-Investigator: Joon Ho Moon, MD.         
Yeungnam University College of Medicine Recruiting
Daegu, Korea, Republic of
Contact: Lee       leehj0330@yahoo.co.kr   
Principal Investigator: Min Kyoung Kim, MD, PhD         
Sub-Investigator: Myung Soo Hyun, MD, PhD         
Chungnam National University Hospital Recruiting
Daejeon, Korea, Republic of
Contact: Lee       ljy99@cnuh.co.kr   
Principal Investigator: Deog-Yeon Jo, MD, PhD         
Sub-Investigator: Ik-Chan Song, MD         
Asan Medical Center, University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Ji-Young Min, RN       miracleminjy@naver.com   
Principal Investigator: Dae-Young Kim, MD         
Sub-Investigator: Kyoo-Hyung Lee, MD, PhD         
Sub-Investigator: Je-Hwan Lee, MD, PhD         
Sub-Investigator: Jung-Hee Lee, MD, PhD         
Sub-Investigator: Yunsuk Choi, MD         
Sub-Investigator: Young-Hun Park, MD         
Chung-Ang University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Park       danapark2010@gmail.com   
Principal Investigator: Eunkyung Park, MD, PhD         
Sub-Investigator: Hee Jun Kim, MD, PhD         
Ewha Womans University Mokdong Hospital Recruiting
Seoul, Korea, Republic of
Contact: Ryoo       emhcrc@gmail.com   
Principal Investigator: Yeung-Chul Mun, MD, PhD         
Sub-Investigator: Hyun-Kyung Kim, MD, PhD         
Konkook University Hospital Withdrawn
Seoul, Korea, Republic of
Korea University Anam Hospital Recruiting
Seoul, Korea, Republic of
Contact: Song    82-2-920-5983    hema5983@kumc.or.kr   
Principal Investigator: Yong Park, MD         
Sub-Investigator: Byung Soo Kim, MD, PhD         
Samsung Medical Center Withdrawn
Seoul, Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Park       keira79@paran.com   
Principal Investigator: Inho Kim, MD, PhD         
Sub-Investigator: Byoung Kook Kim, MD, PhD         
Sub-Investigator: Seonyang Park, MD, PhD         
Sub-Investigator: Sung-Soo Yoon, MD, PhD         
Sub-Investigator: Ji Hyun Kwon, MD         
Soonchunhyang University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Lim       s2916@schmc.ac.kr   
Principal Investigator: Jong-Ho Won, MD, PhD         
Sub-Investigator: Kyoung Ha Kim, MD, PhD         
Ulsan University Hospital, University of Ulsan College of Medicine Recruiting
Ulsan, Korea, Republic of
Contact: Kim       miyoung3798@yahoo.co.kr   
Principal Investigator: Hawk Kim, MD, PhD         
Sub-Investigator: Jae Hoo Park, MD, PhD         
Sponsors and Collaborators
Asan Medical Center
Principal Investigator: Young Don Joo, MD, PhD Inje University
Study Director: Dae-Young Kim, MD Asan Medical Center
  More Information


Responsible Party: Dae-Young Kim, Associate Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01429610     History of Changes
Other Study ID Numbers: KALLA0804 
Study First Received: August 30, 2011
Last Updated: July 1, 2015
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
acute lymphoblastic leukemia

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2016