Sequential Intensive Chemotherapy Followed by RIC for Refractory and Relapse AML

Sequential Intensive Chemotherapy Followed by Allogeneic Stem Cell Transplantation With Reduce-intensity Conditioning for Refractory and Relapse Acute Myeloid Leukemia in Adult Patients

Patients with refractory and relapse leukemia had poor outcome even with allogeneic stem cell transplantation. In our previous retrospective study, the overall survival is 14.6+/-8.8% while 90% patients eventually relapsed with marrow ablative conditioning mostly standard iv-Bu-Cy or Cy-TBI. The accumulated TRM is 29.5+/-11.5%. Thus our data suggested that the conventional transplantation approach may not be able to overcome the refractory disease. A new strategy to combined a low dose regimen following intensive chemotherapy for tumor reduction seems to be effect in both relapsed. high-risk and refractory AML or ALL. In this study, we focus on a new treatment strategy for particular refractory AML patients.

Study Overview

• Status: Completed
• Conditions: Acute Leukemia
• Intervention / Treatment: Drug: intensive chemo - RIC preparation

Detailed Description

This is a single arm phase II trial to test the efficacy and feasibility of new sequential intensive chemo and transplantation approach for refractory leukemia. Patients with refractory acute myeloid or lymphoblastic leukemia are enrolled in this trial. Patients will received intensive chemotherapy including Fludarabine, cytarabine and idarubicin as (FLAG-IDA). Seven days after the chemotherapy, sequential transplantation conditioning regimen as fludarabine and busulfan will be given.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200025
    • Blood & Marrow Transplantation Center, RuiJin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients with refractory or relapse acute myeloid leukemia not in remission after 2 cycles of induction chemotherapy early relapse (1st remission less than 6 months) not in remission after 1 cycle of re-induction chemotherapy multiple relapse
• age 16-60 years
• with inform consent
• no contraindication for allogeneic transplantation: active infection, allergy to FLu/Bu/CTX, liver and renal function damage
• HLA matched related (6/6) or unrelated donors (at least 8/10)

Exclusion Criteria:

• age less than 18 years or over 61 years
• liver function/renal function damage (over 2 X upper normal range)
• with mental disease

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: intensive chemo - RIC preparation; The intensive chemotherapy is composed of Fludarabine 35mg/m2 D1-5, high-dose cytarabine 2g/m2 D1-5 + idarubicin (12mg/m2) D5-7. The reduced intensity preparation regimen will start 7 days after the chemotherapy with fludarabine 35mg/m2 for 5 days + iv busulfan 3.2mg/kg/day for 3 days followed by stem cell infusion 2 days later.	Drug: intensive chemo - RIC preparation; The intensive chemotherapy is composed of fludarabine 35mg/m2 + high-dose cytarabine 2g/m2 D1-5 + idarubicin (12mg/m2) D5-7. The reduced intensity preparation regimen will start 7 days after the chemotherapy with fludarabine 35mg/m2 for 5 days + iv busulfan 3.2mg/kg/day for 3 days followed by stem cell infusion 2 days later.; Other Names: FLAG-IDA-RIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival	2-year

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	2-year
non-relapse mortality	2-year
relapse rate	2-year

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Jiong HU, M.D., Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Tang W, Fan X, Wang L, Hu J. Busulfan and fludarabine conditioning regimen given at hematological nadir of cytoreduction fludarabine, cytarabine, and idarubicin chemotherapy in patients with refractory acute myeloid leukemia undergoing allogeneic stem cell transplantation: a single arm pilot consort study. Medicine (Baltimore). 2015 Apr;94(15):e706. doi: 10.1097/MD.0000000000000706.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: December 19, 2011
• First Submitted That Met QC Criteria: December 19, 2011
• First Posted (Estimate): December 21, 2011

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: allogeneic stem cell transplantation; RIC regimen; intensive chemotherapy; feasibility, effective and safety; refractory or relapse leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Recurrence
• Other Study ID Numbers: RJH-2011-RefactoryAML-SCT

Plan for Individual participant data (IPD)

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