The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
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| ClinicalTrials.gov Identifier: NCT02745717 |
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Recruitment Status :
Recruiting
First Posted : April 20, 2016
Last Update Posted : April 20, 2020
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Aim: To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving immunosuppressive therapy (IST).
Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group
Treatment:
IST group: ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A (CSA) Cord blood transfusion group: In addition to the same dose and course of ATG and CSA , one unit of cord blood having no more than 2 HLA-A, B or DRB1 mismatches is transfused 24h after last dose of ATG administration.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Severe Aplastic Anemia | Drug: Thymoglobulin Procedure: Cord blood Drug: Cyclosporine Oral Product | Phase 4 |
Eligible patients should be under 60 years old with confirmed SAA, without HLA matched siblings and previous ATG treatment history. Patients will be excluded if they present any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al or severely allergic to biologic products.
To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving IST therapy, 120 eligible patients will be randomized to two groups, the IST group and the cord blood transfusion group. Patients in the IST group receive standard IST which including ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A（CSA ) started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml. While patients in the cord blood transfusion group receive the same dose and course of ATG and CSA as the control group and one unit of cord blood having no more than 2 HLA-A, B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
The neutrophil recovery day is defined as the first day of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×109/L, without G-CSF adminstration. Platelet recovery day is defined to have occurred on the first of 7 consecutive days with a blood platelet count (BPC) of >20×109/L, without transfusion support. Response (CR, PR or NR) is evaluated on 3, 4, 6,9, 12, 18 and 24months after treatment.
The primary end point is the neutrophil recovery day and second end points are response rate (CR+PR), treatment related mortality, disease free survival and overall survival.
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| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 120 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia |
| Actual Study Start Date : | January 2016 |
| Estimated Primary Completion Date : | December 2021 |
| Estimated Study Completion Date : | December 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: cord blood and IST group
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
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Drug: Thymoglobulin
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
Other Name: Thymoglobuline Procedure: Cord blood transfusion of one unit of at least 4/6 HLA loci matched cord blood. Drug: Cyclosporine Oral Product administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
Other Name: cyclosporine A |
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Active Comparator: IST group
Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.
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Drug: Thymoglobulin
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
Other Name: Thymoglobuline Drug: Cyclosporine Oral Product administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
Other Name: cyclosporine A |
- neutrophil recovery day [ Time Frame: 5 days to 365 days ]
the first day of 3 consecutive days when the absolute neutrophil count (ANC) reaches 0.5×10^9/L, without G-CSF administration .
The day of first dose of ATG administration is record as day 0.
- overall response rate [ Time Frame: 3 months to 24 months ]overall response rate is the percentage of patients who acquire complete remission and partial remission according to the criteria of British Committee for Standards in Haematology (BCSH).
- overall survival [ Time Frame: 24month ]The length of time from the start of treatment for patients with SAA are still alive.
- Treatment related mortality [ Time Frame: 3months, 24months ]The death rate of patients because of treatment
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| Ages Eligible for Study: | up to 60 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
1．Diagnosis of AA confirmed by bone marrow aspirate and biopsy, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria were excluded. To confirm severe AA, the patient must fulfill at least two of the criteria: i) ANC<0.5×109/L,ii)PLT<20×109/L and iii) Ret<20×109/L ,in addition, ANC<0.5×109/L must be included.
2. Under 60 years old, male or female.
3. No HLA matched siblings.
4. No previous ATG treatment history.
5. Performance status score no more than 2 (ECOG criteria).
6．Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal) Serum creatinine and BUN <1.25×ULN.
7. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
8．Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
9. Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
- Presence of any condition inappropriate for HSCT.
- Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
3．Severely allergic to biologic products.
4．Pregnancy or breastfeeding.
5．Current treatment on another clinical trail.
6．Any other condition the investigator judged the patient inappropriate for entry into this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02745717
| Contact: Jieling Jiang, M.D. | 86-21-37798987 | jiangjieling66@hotmail.com | |
| Contact: Liping Wan, M.D.,Ph. D. | 86-21-63240090 ext 3921 | wanliping924@hotmail.com |
| China, Shanghai | |
| Shanghai general hospital, Shanghai Jiaotong university school of medicine | Recruiting |
| Shanghai, Shanghai, China, 200080 | |
| Contact: Xingpeng Wang, M.D., Ph.D. 86-21-63069298 sfph_edu2@163.com | |
| Contact: Yanhong Zhu, M.S 86-21-63240090 ext 6213 sfph_edu2@shumu.edu.cn | |
| Sub-Investigator: Jieling Jiang, M.D. | |
| Principal Investigator: | Chun Wang, M.D., Ph. D. | Shanghai General Hospital, Shanghai Jiaotong University School of Medicine |
| Responsible Party: | Chun Wang, director, department of hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT02745717 |
| Other Study ID Numbers: |
Shanghai1st-48 |
| First Posted: | April 20, 2016 Key Record Dates |
| Last Update Posted: | April 20, 2020 |
| Last Verified: | April 2020 |
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Severe aplastic anemia immunosuppressive therapy cord blood transfusion |
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Anemia Anemia, Aplastic Hematologic Diseases Bone Marrow Diseases Cyclosporine Cyclosporins Thymoglobulin Antilymphocyte Serum Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Dermatologic Agents Antirheumatic Agents Calcineurin Inhibitors |