Efficacy and Safety of MTBF Conditioning Regimen for Salvageable Allo-HSCT in the Treatment of R/R AML

Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

Efficacy and Safety of Mitoxantrone Hydrochloride Liposome Combined With Thiotepa, Busulfan and Fludarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06385808
• Other study ID #: XJTU1AF-CRF-2023-XK014
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Xiaoning Wang, M.D.
• Phone: 0086-18991232608
• Email: wangxn99[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to evaluate the efficacy of MTBF conditioning regimen of salvageable allo-HSCT in patients with relapsed or refractory acute myeloid leukemia. The secondary purpose of the study was to observe the safety of MTBF regimen in these patients.

Description:

High-intensity conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) can maximize the clearance of leukemia cells, but is often associated with increased pretreatment-related toxicity and transplant-related mortality. In order to enhance its anti-tumor effect without increasing or even decreasing its tissue toxicity, and then prolong the overall survival of AML patients, we optimized the conditioning regimen before allo-HSCT transplantation: (1) The classical Thiotepa/Busulfan/Fludarabine (TBF) regimen will be adopted to reduce the conditioning associated toxicity, ensure graft implantation to the maximum extent and reduce the recurrence rate; ② At the same time, mitoxantrone hydrochloride liposome will be added to avoid the disadvantages of weak immunosuppressive effect and weak anti-leukemia effect, and MTBF pretreatment scheme will be finally explored. It has been applied in the pre-treatment of salvage allo-HSCT in 3 patients with relapsed and refractory acute myeloid leukemia with good safety. Up to the present follow-up time of 4 months, all 3 patients have disease free survival. To evaluate the safety and efficacy of this protocol, we intend to include more patients undergoing salvage allo-HSCT for relapsed or refractory (R/R) AML.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 37
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with the follow-up;
• Age 18-65 years old (including upper and lower limits);
• No gender limitation
• Relapsed or refractory (R/R) acute myeloid leukemia can not achieve complete remission by chemotherapy, and has the indication of salvage allogeneic hematopoietic stem cell transplantation.
• R/R AML was defined as: ? Initial treatment cases that failed after 2 courses of standard chemotherapy; ? After CR consolidation and intensive treatment, relapse within 12 months; ? Recurred 12 months later, but conventional chemotherapy was ineffective; ? Two or more relapses; ? Extramedullary leukemia persists; ?Leukemia cells in peripheral blood or the proportion of bone marrow original cells >0.050 or the occurrence of extramedullary leukemia cell infiltration after CR.
• Could tolerate allogeneic hematopoietic stem cell transplantation.

Exclusion Criteria:

• Hypersensitivity to any investigational drug or its components;
• Uncontrolled systemic diseases (e.g. active infections, uncontrolled hypertension, diabetes, etc.)
• Cardiac function and disease meet one of the following conditions:

1. Long QTc syndrome or QTc interval>480 ms;

2. Complete left bundle branch block, II or III degree atrioventricular block;

3. Serious and uncontrolled arrhythmia requiring drug treatment;

4. American New York Heart Association rating = III degree;

5. Cardiac ejection fraction (LVEF) is less than 60%;

6. History of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or He has any arrhythmia requiring treatment, clinical history of serious pericardial disease, or acute ischemia or activity ECG evidence of abnormal conduction system;

• Active infection of hepatitis B and hepatitis C;
• Human immunodeficiency virus (HIV) infection;
• Patients with other malignant tumors;
• History of drug abuse (non-medical use of narcotic drugs or psychotropic drugs) or history of drug dependence (sedative hypnotics, analgesics, narcotics, stimulants and psychotropic drugs, etc.);
• History of mental illness or cognitive impairment;
• Other investigators determined that participation in this study was not appropriate.

Related Conditions & MeSH terms

• Conditioning
• Hematopoietic Stem Cell Transplantation
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory Acute Myeloid Leukemia
• Relapse Leukemia

Intervention

Drug:
• MTBF regimen
The subjects will be treated with mitoxantrone hydrochloride liposome combined with thiotepa, busulfan and fludarabine as conditioning regimen prior to allo-HSCT. Mitoxantrone hydrochloride liposome 24mg/m^2 ivgtt d-7; Ctepide 5mg/kg ivgtt d-6~-5; Busulfan 0.8mg/kg q6h ivgtt d-4~-2; Fludarabine 50mg/m^2 ivgtt d-4~-2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	aGVHD	The incidence of acute graft versus host disease	At day 100 post transplantation
Primary	Recurrence rate	Disease activity in patients after transplantation	2 years post transplantation
Secondary	Incidence and Severity of non-hematological adverse events (NCI CTCAE v5.0)	The incidence and severity of non-hematological adverse events were evaluated using NCI CTCAE v5.0 criteria.	from the beginning of the conditioning regimen to 2 years post transplantation
Secondary	Neutrophil recovery time	Peripheral blood neutrophil count (ANC) =0.5×10^9/L for three consecutive days without blood transfusion support	1 month post transplantation
Secondary	Platelet recovery time	Peripheral blood platelet (PLT) =20×10^9/L for three consecutive days without blood transfusion support.	1 month post transplantation
Secondary	OS	Overall survival	From date of diagnosis until the end of follow-up or the date of death from any couse. Time rage: 6 months post transplantation, 12 months post transplantation.
Secondary	PFS	Progression-free survival	From date of diagnosis until the end of follow-up or disease progression. Time rage: 6 months post transplantation, 12 months post transplantation.