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

Phase 2
15 Years
Open (Enrolling)
Precursor Cell Lymphoblastic Leukemia-Lymphoma

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Trial Information

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

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

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.

Inclusion Criteria:

- Patients who were previously untreated and had either ALL or high-risk lymphoblastic

- Ph(-) on chromosome analysis by conventional G-band technique and/or BCR-ABL(-) by
PCR method

- Patients whose leukemic blast cells express ≥20% of CD20 antigens at time of

- No prior chemotherapy for leukemia (use of hydroxyurea or leukapheresis are

- 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)

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

relapse-free survival (RFS) rate

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Young Don Joo, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Inje University


South Korea: Korea Food and Drug Administration (KFDA)

Study ID:




Start Date:

November 2011

Completion Date:

October 2015

Related Keywords:

  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • acute lymphoblastic leukemia
  • rituximab
  • VPDL
  • CD20
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma