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AzTrials

Precursor Cell Lymphoblastic Leukemia-LymphomaPhase 2RADICALNCT01429610

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

A Phase 2 study testing Rituximab+mVPDL in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma, run by Asan Medical Center at 19 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Rituximab+mVPDL
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
19 sitesSouth Korea
Study dates
Nov 2011to 1 Jan 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
Show all 10Show fewer
  • 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.

Who cannot join

  • 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)

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

South Korea19 sites

  • Division of Hematology-Oncology, Dong-A University College of Medicine

    Busan

  • Dong-A University College of Medicine

    Busan

  • Inje University Busan Paik Hospital

    Busan

  • Inje University Haeundae-Paik Hospital

    Busan

  • Kosin University College of Medicine, Kosin University Gospel Hospital

    Busan

  • Catholic University of Daegu School of Medicine

    Daegu

  • Keimyung University Dongsan Medical Center

    Daegu

  • Kyungpook National Unviersity Hospital

    Daegu

  • Yeungnam University College of Medicine

    Daegu

  • Chungnam National University Hospital

    Daejeon

  • Chonnam National University Hwasun Hospital

    Hwasun, Chollanamdo

  • Hematologic Oncology Clinic, National Cancer Center

    Ilsan, Kongki

  • Asan Medical Center, University of Ulsan College of Medicine

    Seoul

  • Chung-Ang University Hospital

    Seoul

  • Ewha Womans University Mokdong Hospital

    Seoul

  • Korea University Anam Hospital

    Seoul

  • Seoul National University Hospital

    Seoul

  • Soonchunhyang University Hospital

    Seoul

  • Ulsan University Hospital, University of Ulsan College of Medicine

    Ulsan

Other trials in South Korea

About this study

Official title: 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.

Read the 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.

Being tested
Rituximab+mVPDL
Keywords
acute lymphoblastic leukemia, rituximab, VPDL, CD20
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rituximab+mVPDLDrug

    Also called Mabthera, VCS, Daunobrastina, Solondo

    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)
    1. 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)
    1. 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
    1. 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)
    1. 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
    1. Consider alloHCT
Study groups in NCT01429610
Study groupRoleWhat they receive
Rituximab+mVPDLExperimentalPatients who were CD20(+), newly-diagnosed adult ALL and treated with rituximab + mVPDL treatment plan
Receives: Drug: Rituximab+mVPDL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. relapse-free survival (RFS) rate

    Measured: 2 years

Secondary outcomes (4)

  1. complete remission (CR) rates

    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

    Measured: 4 weeks (from the initiation of induction treatment)

  2. relapse-free survival rates

    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.

    Measured: 2 years

  3. overall survival rates

    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.

    Measured: 2 years

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

    among alloHCT recipients

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2011 (estimated)
  2. Study startNov 2011
  3. Primary completion1 Jan 2018
  4. Study completion1 Jan 2019 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01429610
Sponsor's protocol ID
KALLA0804
Acronym
RADICAL
Status last verified
Jul 2018
First submitted
30 Aug 2011
Last updated
24 Jul 2018
Results posted
No
Data monitoring committee
No

Publications

  • Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003 Mar 1;21(5):774-80. doi: 10.1200/JCO.2003.02.053. Epub 2003 Mar 1.

    PubMed 12610173

  • Hallbook H, Gustafsson G, Smedmyr B, Soderhall S, Heyman M; Swedish Adult Acute Lymphocytic Leukemia Group; Swedish Childhood Leukemia Group. Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006 Oct 1;107(7):1551-61. doi: 10.1002/cncr.22189.

    PubMed 16955505

  • Todeschini G, Tecchio C, Meneghini V, Pizzolo G, Veneri D, Zanotti R, Ricetti MM, Solero P, April F, Perona G. Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin. Leukemia. 1998 Feb;12(2):144-9. doi: 10.1038/sj.leu.2400912.

    PubMed 9519775

  • Thomas D, O'Brien S, Faderl S, Ravandi F, Jabbour E, Pierce S, Cortes J, Kantarjian H. Anthracycline dose intensification in adult acute lymphoblastic leukemia: lack of benefit in the context of the fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen. Cancer. 2010 Oct 1;116(19):4580-9. doi: 10.1002/cncr.25319.

    PubMed 20572037

  • Tomblyn MB, Arora M, Baker KS, Blazar BR, Brunstein CG, Burns LJ, DeFor TE, Dusenbery KE, Kaufman DS, Kersey JH, MacMillan ML, McGlave PB, Miller JS, Orchard PJ, Slungaard A, Tomblyn MR, Vercellotti GM, Verneris MR, Wagner JE, Weisdorf DJ. Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. J Clin Oncol. 2009 Aug 1;27(22):3634-41. doi: 10.1200/JCO.2008.20.2960. Epub 2009 Jul 6.

    PubMed 19581540

  • Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.

    PubMed 19179301

  • Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. doi: 10.1182/blood-2007-10-116582. Epub 2007 Nov 29.

    PubMed 18048644

  • Pituch-Noworolska A, Hajto B, Mazur B, Sonta-Jakimczyk D, Balwierz W, Janota-Krawczyk E, Kowalska H, Malinowska I, Modzelewska M, Wasik M. Expression of CD20 on acute lymphoblastic leukemia cells in children. Neoplasma. 2001;48(3):182-7.

    PubMed 11583286

  • Maury S, Huguet F, Leguay T, Lacombe F, Maynadie M, Girard S, de Labarthe A, Kuhlein E, Raffoux E, Thomas X, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Rousselot P, Macintyre E, Ifrah N, Dombret H, Bene MC; Group for Research on Adult Acute Lymphoblastic Leukemia. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica. 2010 Feb;95(2):324-8. doi: 10.3324/haematol.2009.010306. Epub 2009 Sep 22.

    PubMed 19773266

  • Borowitz MJ, Shuster J, Carroll AJ, Nash M, Look AT, Camitta B, Mahoney D, Lauer SJ, Pullen DJ. Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study. Blood. 1997 Jun 1;89(11):3960-6.

    PubMed 9166833

  • Jeha S, Behm F, Pei D, Sandlund JT, Ribeiro RC, Razzouk BI, Rubnitz JE, Hijiya N, Howard SC, Cheng C, Pui CH. Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2006 Nov 15;108(10):3302-4. doi: 10.1182/blood-2006-04-016709. Epub 2006 Aug 8.

    PubMed 16896151

  • Thomas DA, O'Brien S, Jorgensen JL, Cortes J, Faderl S, Garcia-Manero G, Verstovsek S, Koller C, Pierce S, Huh Y, Wierda W, Keating MJ, Kantarjian HM. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood. 2009 Jun 18;113(25):6330-7. doi: 10.1182/blood-2008-04-151860. Epub 2008 Aug 14.

    PubMed 18703706

  • Al Gwaiz LA, Bassioni W. Immunophenotyping of acute lymphoblastic leukemia using immunohistochemistry in bone marrow biopsy specimens. Histol Histopathol. 2008 Oct;23(10):1223-8. doi: 10.14670/HH-23.1223.

    PubMed 18712674

  • Claviez A, Eckert C, Seeger K, Schrauder A, Schrappe M, Henze G, von Stackelberg A. Rituximab plus chemotherapy in children with relapsed or refractory CD20-positive B-cell precursor acute lymphoblastic leukemia. Haematologica. 2006 Feb;91(2):272-3.

    PubMed 16461321

  • Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. doi: 10.1002/cncr.21776.

    PubMed 16502413

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab+mVPDL in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma, run by Asan Medical Center at 19 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

relapse-free survival (RFS) rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01429610, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.

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