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

July 22, 2018 updated by: Je-Hwan Lee, Asan Medical Center

Phase 2 Study Evaluating the Efficacy of Rituximab Plus Modified VPDL for Newly Diagnosed CD20-Positive Adult Acute Lymphoblastic Leukemia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Cytarabine
  • Mabthera
  • Leunase
  • VCS
  • Daunobrastina
  • Solondo
  • Efosin
  • DBLMethotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
relapse-free survival (RFS) rate
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 weeks (from the initiation of induction treatment)
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.
2 years
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.
2 years
Cumulative incidence and maximal severity of acute / chronic graft-versus-host disease
Time Frame: 2 years
among alloHCT recipients
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (Actual)

January 1, 2018

Study Completion (Anticipated)

January 1, 2019

Study Registration Dates

First Submitted

August 30, 2011

First Submitted That Met QC Criteria

September 3, 2011

First Posted (Estimate)

September 7, 2011

Study Record Updates

Last Update Posted (Actual)

July 24, 2018

Last Update Submitted That Met QC Criteria

July 22, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KALLA0804

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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