Pegylated Liposomal Doxorubicin Versus Daunorubicin to Treat Acute Lymphoblastic Leukemia:

Pegylated Liposomal Doxorubicin-contained Versus Daunorubicin-contained VDCLD Regimen in Previously Untreated Adult Patients With Acute Lymphoblastic Leukemia: Complete Remission Rates and Changes of Leukemia Stem Cells

To determine, compared with Daunorubicin(DNR), whether Pegylated liposomal doxorubicin (PLD) inducing higher complete remission (CR) rate, in untreated primary ALL adult patients with VDCLD regimen induction therapy. Second, to determine, compared with the DNR, whether chemotherapy containing PLD with a higher response rates and greater safety in adult ALL

Study Overview

• Status: Unknown
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: VDCLD regimen

Detailed Description

This is a prospective, multicenter, open, non-intervention clinical study, with estimated enrollment of 200 newly diagnosed adult ALL patients. After the first course of treatment administered with PLD-contained or DNR-contained VDCLD regimen, CR rate and changes of leukemia stem cells in bone marrow, was evaluated; the safety of these chemotherapy was also evaluated.

Study Patients:

Patients included in this study should be untreated with ALL previously, being in line with the inclusion criteria and exclusion criteria.

Dosage and Administration:

PLD-contained VDCLD regimen：PLD 36 mg/m2 ivdrip over 60 minutes( d1、15),VCR 1.4mg/m iv(d1，8，15，22), CTX 800 mg/m2 ivdrip( d1), L-asp 6000u/m2 ivdrip(d19～28),Dex10mg ivdrip (d1～28).

DNR-contained VDCLD regimen：DNR 45 mg/m2 ivdrip over 60 minutes(d1～3),VCR 1.4mg/m2 iv(d1，d8，d15，d22), CTX 800 mg/m2 ivdrip(d1), L-asp 6000u/m2 ivdrip(d19～28),Dex10mg ivdrip(d1～28).

Endpoints:

Primary endpoint: The primary endpoint of the study was complete remission (CR) rates after the first course of regimen. The proportion of patients achieved CR was evaluated, after the first course of induction chemotherapy administered with PLD-contained or DNR-contained VDCLD regimen Secondary endpoint: The change of leukemia stem cells in bone marrow, was evaluated before and after administered with PLD-contained or DNR-contained VDCLD regimen.

Safety Assessment:

In order to adjust the treatment strategy and ensure patients' safety effectively, routine blood test, transaminases, and creatinine was monitored on time during the period, while lung CT and ECG was performed based on clinical need. Possible adverse reactions and tolerability during treatment, such as gastrointestinal reactions, cardiac function, as well as discontinuation ratio due to side effects or tolerability of PLD, was recorded.

Statistical Analysis:

All the calculations were performed with the SPSS statistical software. The continuous variables were performed with T test; categorical variables were performed withχ2 test. After acceptance of various observation records sheets, data were unified processed.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Zhanjiang, Guangdong, China, 524000
      • Recruiting
      • Department of Hematology, Affiliated Hospital of Guangdong Medical College
      • Contact: Yang Zhi gang; Phone Number: +86 13560512702; Email: 13560512702@139.com
      • Principal Investigator: Zhi gang Yang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Eligible men or women were age over 14，but less than 60 years;

Eastern Cooperative Oncology Group performance status of 0 to2;

Diagnosed with ALL (WHO classification, the primitive cells ≥ 20%);

Previous untreated ALL patients had not received chemotherapy before (excluding dexamethasone, prednisone, and hydroxyurea). History of receiving blood transfusion, hematopoietic growth factors, vitamin, and palliative measures such as leukocyte removal, dexamethasone, prednisone, hydroxyurea (0.5-3g daily, more than three days) is allowed;

The levels of LSCs in bone marrow were measured with flow cytometry before treatment;

Subjects must be able to provide written informed consent.

Exclusion Criteria:

Mixed type of AL patients;

Clinically significant active infections;

Nursing (breastfeeding) or intending to be nursing during the study；

Pregnancy, or intending to become pregnant during the study;

Patients with cardiac dysfunction currently (especially congestive heart failure) or history of congestive heart failure;

Patients with severe liver failure (ALT ≥ 5 times the upper limit of normal (ULN), total bilirubin ≥ 3mg/dL)

Patients with renal insufficiency, creatinine clearance <30ml/min, creatinine clearance rate is calculated as follows: Men: Ccr (ml / min) = (140 - age) × weight (kg) / [0.8136 × serum creatinine (μmol / L )] female: Ccr (ml / min) = (140 - age) × weight (kg) × 0.85 / [0.8136 × serum creatinine (μmol / L)];

Patients did not or will not participate in other trials of drugs 30 days before or 90 days after the beginning of this study,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PLD-contained VDCLD regimen; PLD 36 mg/m2 ivdrip over 60 minutes( d1、15),VCR 1.4mg/m iv(d1，8，15，22), CTX 800 mg/m2 ivdrip( d1), L-asp 6000u/m2 ivdrip(d19～28),Dex10mg ivdrip (d1～28).	Drug: VDCLD regimen
ACTIVE_COMPARATOR: DNR-contained VDCLD regimen; DNR 45 mg/m2 ivdrip over 60 minutes(d1～3),VCR 1.4mg/m2 iv(d1，d8，d15，d22), CTX 800 mg/m2 ivdrip(d1), L-asp 6000u/m2 ivdrip(d19～28),Dex10mg ivdrip(d1～28).	Drug: VDCLD regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rates after the first course of regimen	The primary endpoint of the study was complete remission (CR) rates after the first course of regimen. The proportion of patients achieved CR was evaluated, after the first course of induction chemotherapy administered with PLD-contained or DNR-contained VDCLD regimen	3 years after the last enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of leukemia stem cells in bone marrow	The change of leukemia stem cells in bone marrow, was evaluated before and after administered with PLD-contained or DNR-contained VDCLD regimen.	3 years after the last enrollment

Collaborators and Investigators

• Sponsor: Changzhou Jinyuan Pharmaceutical Manufacturing Co., Ltd.
• Collaborators: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Zhigang Yang, The Affiliated Hospital of Guangdong Medical College

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ANTICIPATED): November 1, 2015
• Study Completion (ANTICIPATED): December 1, 2015

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: February 23, 2014
• First Posted (ESTIMATE): February 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 6, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: ChangzhouJP