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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier:
NCT01457040
First received: October 11, 2011
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Stem Cell Transplantation, Hematopoietic
Other: TBI/CY/VP-16
Other: FA-TBI/CY/VP-16
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Study of Intensified Conditioning Regimen With High-Dose-Etoposide for Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in China

Resource links provided by NLM:


Further study details as provided by Nanfang Hospital of Southern Medical University:

Primary Outcome Measures:
  • Over Survival [ Time Frame: 3 years after HSCT ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Relapse-Free-Survival [ Time Frame: 3 years after HSCT ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: October 2011
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: First Complete Remission of ALL
CR1 Cohort: subject with ALL in First Complete Remission (CR)
Other: TBI/CY/VP-16
CR1 Cohort will receive condition 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-First Complete Remission
Non-CR1 Cohort: subject with ALL beyond first CR, or not remission
Other: FA-TBI/CY/VP-16
Non-CR1 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

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.

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 16 years to 65 years
  2. Diagnosis of acute lymphoblastic leukemia
  3. Disease condition in CR1 or Non-CR1
  4. Patient received allogeneic hematopoietic stem cell transplantation
  5. The informed consent form has been signed.
  6. The following exclusion criteria are excluded.

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01457040

Locations
China, Guangdong
Department of Hematology, Nanfang Hospital
Guangzhou, Guangdong, China, 510515
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Investigators
Principal Investigator: Qifa Liu, MD Department of Hematology, Nanfang Hospital
  More Information

Publications:

Responsible Party: Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT01457040     History of Changes
Other Study ID Numbers: HDE-ALL-2011
Study First Received: October 11, 2011
Last Updated: October 29, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Nanfang Hospital of Southern Medical University:
Acute Lymphoblastic leukemia
Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Etoposide
Etoposide phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014