Efficacy and Safety of Azacitidine Combined With Interferon in the Treatment of Post-transplant Recurrence

Efficacy and Safety of Azacitidine Combined With Interferon in the Treatment of Recurrence of Allogeneic Hematopoietic Stem Cell Transplantation in Myeloid Tumors of the Blood System

This study is a single-center, one-arm, prospective, phase II clinical trial with the primary objective of assessing the effectiveness of azacitidine combined with interferon in the prevention of recurrence after allogeneic transplantation of myeloid tumors (AML/MDS/MPN) in the blood system. Sex and safety.

At the screening/baseline period, informed consent is obtained and the inclusion/exclusion criteria are checked. Plan to enroll 30 patients, and collect demographic data, medical history data, vital signs, physical examination, laboratory tests (hematuria, liver and kidney function; immune indicators: T cell subsets, Treg, etc.), pregnancy test for female patients And other necessary auxiliary inspections.

The time to start treatment is: a decrease in chimerism and/or minimal residual disease (MRD) after myeloid tumor allogeneic hematopoietic stem cell transplantation.

Study Overview

• Status: Unknown
• Conditions: Efficacy and Safety; HSCT
• Intervention / Treatment: Drug: Azacitidine combined with interferon preemptive treatment

Detailed Description

Treatment programs:

1. Basic protocol: Azacitidine is administered subcutaneously at 32 mg/m2/d for 5 consecutive days; α-interferon treatment started on day 8 for 3 weeks; 4-6 weeks/treatment with long-acting interferon Gebin). 1-1.5 million U / kg, once a week; or ordinary alpha-interferon, 200 acres / square meter / d (total ≥ 300MU / d), 5-7 days a week;
2. Start time of medication:

1 In the absence of immunosuppressive agents such as cyclosporine, the chimeric rate is decreased and/or MRD-positive: or in the case of immunosuppressive agents such as cyclosporine, the chimeric rate is fully chimeric and MRD-positive: A-interferon is first administered. Single-agent intervention, if there was no significant decrease in MRD for 2 consecutive courses (MRD decreased ≤ 50%), azacitidine combined with interferon intervention was started; 2 In the case of calmodulin immunosuppressant (cyclosporine or tacrolimus), the chimeric rate decreased and the MRD was negative, the immunosuppressant was rapidly reduced or discontinued, and the bone marrow was reviewed 2 weeks, if the chimeric rate did not rise. (decreased or stable), or after two consecutive immunosuppressive adjustments did not reach complete chimerism, start azacitidine combined with interferon intervention; (3) If cyclosporine or other immunosuppressive agents are applied before the start of the study, rapid reduction; dose reduction 1 / 4-1 / 2; if the chimeric rate increases or GVHD occurs, continue the immunosuppressant adjustment strategy; (4) Stop treatment: acute GVHD above II degree; patients are intolerant to the study protocol; basic regimen is ineffective after 2 courses of treatment (chimeric rate continues to decline or MRD continues to increase) or disease recurrence; transplant.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongliang Fang, doctor; Phone Number: 021-58552006; Email: fanghongliang@dashengbio.com
• Study Contact Backup: Name: Xianmin Song, M.D; Phone Number: 021-63240090; Email: shongxm@139.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Xianmin Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Patients enrolled must meet the following criteria:

1. ≥ 14 years old, male or female;
2. Patients with allogeneic peripheral blood stem cell transplantation due to myeloid tumors of the blood system (AML/MDS/CML/MPN, etc.);
3. Recurrence trend evaluation criteria: the proportion of bone marrow blast cells <5%; flow cell MRD ≥ 0.01% and interval 2 consecutive times 2 times; fusion gene interval 2 weeks at least 2 consecutive positive and rising trend or from negative to positive; Bone marrow WT1 levels increased dynamically and were greater than 0.6%; chimeric rate (STR) decreased by >5% (STR <90%) or XY-FISH donor chimerism decreased by >0.5%;
4. Blood routine: neutrophils>0.5×109/L, platelets>25.0×109/L;
5. There is no active grade II or higher acute GVHD or moderate or severe chronic GVHD;
6. Liver and kidney function: liver function (AST/ALT/TB) <5 times normal upper limit; renal function (Cr) < 2 times normal upper limit;
7. The patient must be able to understand and be willing to participate in the study and sign an informed consent form.

Exclusion criteria:

Possible subjects who meet any of the following criteria will be excluded from the trial:

1. Recurrence after transplantation;
2. Patients who have not achieved complete remission after transplantation;
3. Implantation failed;
4. Pregnant or lactating women;
5. Have received other interventions or are receiving other research drugs before the study begins;
6. Patient blood routine: ANC <0.5 × 109 / L or PLT < 25 × 109 / L;
7. There are active uncontrolled infections: hemodynamic instability associated with infection, or new signs or signs of infection, or new infections in imaging, persistent fever with asympto or signs cannot be ruled out Infected person
8. People infected with HIV;
9. Active hepatitis B (HBV), active hepatitis C (HCV) requires antiviral therapy; patients with HBV activation risk refer to patients with hepatitis B surface antigen positive or core antibody positive patients who do not receive anti-HBV treatment;
10. Those who are allergic to known azacitidine or interferon;
11. At the discretion of the investigator, other dangerous complications may result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients with recurrence after allogeneic transplantat; One arm	Drug: Azacitidine combined with interferon preemptive treatment; Azacitidine combined with interferon preemptive therapy for prevention and treatment of recurrence of allogeneic transplantation of myeloid tumors (AML/MDS/MPN) in the blood system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response rate	Treatment response rate after 6 months of pretreatment with azacitidine combined with interferon (primary response + secondary response)	6months

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xianmin Song, M.D, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Anticipated): August 28, 2022
• Study Completion (Anticipated): August 28, 2022

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 1, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 24, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: interferon; safety; Efficacy; HSCT; azacitidine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Interferons; Azacitidine
• Other Study ID Numbers: SHSYXY- aza-relapse-2019002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No