Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia

October 11, 2017 updated by: Hongsheng Zhou, Nanfang Hospital of Southern Medical University

A Prospective Study of Intensified Conditioning Regimen With High-Dose-Etoposide for Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in China

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials.

High relapse and transplantation-related-mortality still remains great challenge for HSCT of adult ALL, which both range between 25% and 30%. Recently, risk-adapted indication and optimization of conditioning regimen are highlighted, which aiming to reduce TRM and relapse rate, respectively.City of Hope National Medical Center studied the substitution of etoposide (VP-16) for CY in the treatment of ALL patients receiving HCT. The result suggested that etoposide and TBI are associated with a decreased relapse rate following transplantation for ALL, compared with those receiving CY and TBI. Japanese and Germany reports pronounced the advantage of VP-16 in intensified regimen for adult ALL. On the same time, the investigators previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, the investigators speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the first decade of the new millennium, multiple studies have begun to change our thinking about the treatment of adults with acute lymphoblastic leukemia (ALL). In pediatric patients cure rates in the range of 80% to 90% are now attainable. While adult patients with ALL now have a 90% complete remission (CR) with modern chemotherapy, most patients will relapse, and leukemia-free survival with 3 to 7 years of follow-up in large series is only in the range of 30% to 40%. The poor outcome of chemotherapy in adults with ALL as compared to children relates to multiple factors, including poor tolerance of intensive courses of chemotherapy and a higher incidence of poor prognostic subtypes of ALL such as Philadelphia chromosome-positive ALL and a lower incidence of favorable subtypes such as the t (12; 21).

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. Adult regimens are typically less intense than pediatric regimens. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials. These results have prompted new studies where pediatric ALL regimens have been adapted to the treatment of younger adults. With short follow-up, GRAALL-2003 reports suggest EFS and OS outcomes in the range of 60%. This improved outcome was more pronounced in the standard-risk patients with a donor who had an OS at 5 years of 69%. On the same time, our previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, we speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Department of Hematology, Nanfang Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age: 14 years to 65 years
  2. Diagnosis of High-risk acute lymphoblastic leukemia or standard-risk ALL in ≥CR2
  3. Patient will receive allogeneic hematopoietic stem cell transplantation
  4. The informed consent form has been signed.

Exclusion Criteria:

  1. Patient with severe cardiac dysfunction with less than 50% EF
  2. Patient with severe lung dysfunction
  3. Patient with severe hepatic or renal dysfunction with more than 3 times the upper limit of normal range (ULN) of serum ALT or AST levels, or with more than 2 times the upper limit of normal range (ULN) of serum TBIL level or less than 40% of normal prothrombin time activity (PTA); or with more than 2 times the ULN of serum Cr
  4. Patient with severe active infection
  5. Patient with allergy history about suspected drug in conditioning regimen
  6. Patient with other conditions considered unsuitable for the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Complete Remission (CR)
CR Cohort: high-risk ALL in CR and standard-risk ALL in the status of ≥CR2
Drug: TBI+CY+VP-16
CR Cohort will receive conditioning regimen of TBI+CY+VP-16: TBI: 4.5Gy/d, -5d, -4d; CY: 60mg/kg/d, -3d, -2d; VP-16: 15mg/kg/d, -3d, -2d
EXPERIMENTAL: Non-Remission (NR)
NR Cohort: ALL in non-remission
Drug: FA+TBI+CY+VP-16
NR Cohort will receive conditioning regimen of FA+TBI+CY+VP-16: Flu: 35mg/m2/d: -10~-6d; AraC: 1g/m2/d, -10d~-6d; TBI: 4.5Gy/d, -5d,-4d; CY:60mg/kg/d, -3d, -2d; VP-16: 15mg/kg, -3d, -2d

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Over Survival
Time Frame: 3 years after HSCT
3 years after HSCT

Secondary Outcome Measures

Outcome Measure
Time Frame
Leukemia-Free-Survival
Time Frame: 3 years after HSCT
3 years after HSCT
relapse rate
Time Frame: 3 year
3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital of Southern Medical University

Collaborators

Xiangya Hospital of Central South University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Fujian Medical University Union Hospital

Investigators

  • Principal Investigator: Qifa Liu, MD, Department of Hematology, Nanfang Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2016

Study Registration Dates

First Submitted

October 11, 2011

First Submitted That Met QC Criteria

October 19, 2011

First Posted (ESTIMATE)

October 21, 2011

Study Record Updates

Last Update Posted (ACTUAL)

October 12, 2017

Last Update Submitted That Met QC Criteria

October 11, 2017

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HDE-ALL-2011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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