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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory Acute Myeloid Leukemia; Conditioning; Hematopoietic Stem Cell Transplantation; Relapse Leukemia
• Intervention / Treatment: Drug: MTBF regimen

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoning Wang, M.D.; Phone Number: 0086-18991232608; Email: wangxn99@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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: ① Initial treatment cases that failed after 2 courses of standard chemotherapy; ② After CR consolidation and intensive treatment, relapse within 12 months; ③ Recurred 12 months later, but conventional chemotherapy was ineffective; ④ Two or more relapses; ⑤ Extramedullary leukemia persists; ⑥Leukemia 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.

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: MTBF regimen group; The relapsed or refractory acute myeloid leukemia patients will pretreated with the MTBF regimen prior to salvageable allogeneic hematopoietic stem cells.

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.; Other Names: Fludarabine; Busulfan; Thiotepa; Mitoxantrone Hydrochloride Liposome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	Disease activity in patients after transplantation	2 years post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Platelet recovery time	Peripheral blood platelet (PLT) ≥20×10^9/L for three consecutive days without blood transfusion support.	1 month post transplantation
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.
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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
aGVHD	The incidence of acute graft versus host disease	At day 100 post transplantation

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Principal Investigator: Xiaoning Wang, M.D., First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: allogeneic hematopoietic stem cell transplantation; conditioning regimen; relapsed or refractory acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Fludarabine; Mitoxantrone; Thiotepa; Busulfan
• Other Study ID Numbers: XJTU1AF-CRF-2023-XK014

Drug and device information, study documents

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