Comparison of Liposomal Doxorubicin and Daunorubicin-containing VDCLD Regimen in the Treatment of Adult ALL Patients

Study Overview
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Brief Summary
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This trial is a multicenter prospective, open, non-intervention clinical study. 200 patients with newly diagnosed adult ALL who underwent induction remission with the VDCLD regimen containing PLD and DNR, respectively,were plan to enrolled in this study to evaluate the CR rate and the level of myeloid leukemia stem cells in the first course of chemotherapy with two regimens; and to evaluate the safety of the two induction chemotherapy regimens.

Detailed Description
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Subjects will receive one of two treatment regimens: Group A: intravenous drip of liposomal doxorubicin 36 mg/m2, d1、d15，1h； VCR 1.4mg/m2.d d1，d8，d15，d22 iv，CTX 800mg/m2.d d1 ivdrip，L-asp 6000u/m2.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip，once every 28days. Group B: intravenous drip of DNR45mg/m2，d d1～3，1h；VCR 1.4mg/m2.d d1，d8，d15，d22 iv，CTX 800mg/m2.d d1 ivdrip，L-asp 6000u/m2.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip，once every 28days. The primary endpoint is complete remission after the first course treatment of induced remission chemotherapy, to evaluated the ratio of CR patients after the first course of chemotherapy with PLD and DNR VDCLD regimens.The secondary endpoint is to evaluate the changes of myeloid leukemia stem cells in patients before and after induction of VDCLD with PLD and DNR respectively.

Official Title
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Comparison of Remission Rate and Leukemic Stem Cell Changes Among Patients With Newly Diagnosed Adult ALL With Liposomal Doxorubicin and Daunorubicin-containing VDCLD Regimen.

Conditions
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Adult Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: PLD
* Drug: DNR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Male or female, age:14-60 years old; 2.ECOG score 0-2; 3.Subjects had confirmed ALL (WHO classification, primitive cells ≥ 20%); 4.Patients with newly diagnosed ALL who have not previously received chemotherapy (except for dexamethasone, prednisone, hydroxyurea).Blood transfusion, use of hematopoietic growth factors or vitamins are allowed. Some temporary measures such as leukocyte removal, dexamethasone, prednisone, hydroxyurea (0.5-3g daily, over 3 days) are allowed; 5.Flow cytometry was used to detect leukemic stem cells in bone marrow samples before treatment; 6.Informed consent (all studies must be signed patient informed consent). Exclusion Criteria: 1.Mixed AL patients; 2.Active systemic infection; 3.Lactating women, fertile women with positive pregnancy tests for urine or pregnant women who are unwilling to adopt appropriate methods of contraception (such as the use of birth control pills, intrauterine devices, diaphragms, abstinence, condom use) during the study ; 4. Patients currently have a history of cardiac insufficiency (especially congestive heart failure) or previous history of congestive heart failure; 5. Patients with severe liver failure (≥5 times upper limit of normal transaminase, total bilirubin ≥3 mg/dL); 6. Patients had renal insufficiency with creatinine clearance <30 ml/min and creatinine clearance calculated as follows: Male: Ccr (ml / min) = (140-age) × body weight (kg) / [0.8136 × serum creatinine (μmol/L)] women: Ccr (ml/min) = (140-age) × body weight (kg) × 0.85 / [0.8136 × serum creatinine (μmol/L)]; 7. Patient is involved in other drugs experimental study within 30 days prior to the trial or within 90 days of the start of the trial; 8. Researchers think it is not suitable for enrolling.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VDCLD regimen containing PLD<br>PLD 36mg/㎡.d d1、d15，ivdrip，1h，VCR 1.4mg/㎡.d d1，d8，d15，d22 iv，CTX 800mg/㎡.d d1 ivdrip，L-asp 6000u/㎡.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip | Drug: PLD<br>* PLD36mg/m2.d d1、d15，ivdrip，1h，VCR 1.4mg/m2.d d1，d8，d15，d22 iv，CTX 800mg/m2.d d1 ivdrip，L-asp 6000u/m2.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip<br>* Other names: pegylated liposomal doxorubicin;|
| VDCLD regimen containing DNR<br>DNR 45mg/㎡.d d1～3，ivdrip，1h，VCR 1.4mg/㎡.d d1，d8，d15，d22 iv，CTX 800mg/㎡.d d1 ivdrip，L-asp 6000u/㎡.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip | Drug: DNR<br>* DNR 45mg/m2.d d1～3，ivdrip，1h，VCR 1.4mg/m2.d d1，d8，d15，d22 iv，CTX 800mg/m2.d d1 ivdrip，L-asp 6000u/m2.d d19～28 ivdrip，Dex10mg.d d1～28 ivdrip<br>* Other names: Daunorubicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR | complete remission after the first course treatment of induced remission chemotherapy | From date of randomization until the date of first course of chemotherapy treatment completed, assessed up to 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of myeloid leukemia stem cells | to evaluate the changes of myeloid leukemia stem cells in patients before and after induction of VDCLD with PLD and DNR respectively. | From date of randomization until the date of first course of chemotherapy treatment completed, assessed up to 4 weeks. |