We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01429610
First Posted: September 7, 2011
Last Update Posted: July 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Je-Hwan Lee, Asan Medical Center
  Purpose
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: 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

Resource links provided by NLM:


Further study details as provided by Je-Hwan Lee, Asan Medical Center:

Primary Outcome Measures:
  • relapse-free survival (RFS) rate [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • 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


Enrollment: 78
Study Start Date: November 2011
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01429610


Locations
Korea, Republic of
Chonnam National University Hwasun Hospital
Hwasun, Chollanamdo, Korea, Republic of
Hematologic Oncology Clinic, National Cancer Center
Koyang, Kongki, Korea, Republic of
Division of Hematology-Oncology, Dong-A University College of Medicine
Busan, Korea, Republic of
Dong-A University College of Medicine
Busan, Korea, Republic of
Inje University Busan Paik Hospital
Busan, Korea, Republic of
Inje University Haeundae-Paik Hospital
Busan, Korea, Republic of
Kosin University College of Medicine, Kosin University Gospel Hospital
Busan, Korea, Republic of
Catholic University of Daegu School of Medicine
Daegu, Korea, Republic of
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of
Kyungpook National Unviersity Hospital
Daegu, Korea, Republic of
Yeungnam University College of Medicine
Daegu, Korea, Republic of
Chungnam National University Hospital
Daejeon, Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea, Republic of
Chung-Ang University Hospital
Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital
Seoul, Korea, Republic of
Korea University Anam Hospital
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Soonchunhyang University Hospital
Seoul, Korea, Republic of
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
  More Information

Publications:

Responsible Party: Je-Hwan Lee, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01429610     History of Changes
Other Study ID Numbers: KALLA0804
First Submitted: August 30, 2011
First Posted: September 7, 2011
Last Update Posted: July 21, 2017
Last Verified: July 2017

Keywords provided by Je-Hwan Lee, Asan Medical Center:
acute lymphoblastic leukemia
rituximab
VPDL
CD20

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