Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Study Of NK Cell Transplantation In Newly Diagnosed Acute Myeloid Leukemia
AML08: A Phase II Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Phase II Study Of Natural Killer Cell Transplantation In Patients With Newly Diagnosed Acute Myeloid Leukemia
5 other identifiers
interventional
324
2 countries
8
Brief Summary
The purpose of this study is to assess the feasibility and efficacy of a novel form of therapy-haploidentical NK cell transplantation-in patients with standard-risk AML. In addition, we will investigate the efficacy of clofarabine + cytarabine (Clo/AraC) in newly diagnosed patients with AML and attempt to optimize outcome through the use of MRD-adapted therapy and further improvements in supportive care.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2008
Longer than P75 for phase_3
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 20, 2008
CompletedFirst Posted
Study publicly available on registry
June 24, 2008
CompletedStudy Start
First participant enrolled
August 4, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2017
CompletedResults Posted
Study results publicly available
April 2, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 14, 2020
CompletedAugust 10, 2021
July 1, 2021
8.7 years
June 20, 2008
March 2, 2018
August 6, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Day 22 Minimal Residual Disease (MRD) Measured by Flow Cytometry
MRD-negative is defined as \<0.1% blasts with leukemia-associated phenotype detected by flow cytometry. MRD-positive is defined as \>=0.1% blasts with leukemia-associated phenotype detected by flow cytometry.
Day 22 MRD measurement after one course of therapy
Secondary Outcomes (2)
Event-free Survival of Standard Risk Patients Who Receive Chemotherapy Alone.
3 years after completion of therapy
Event-free Survival of Standard Risk Patients Who Receive Chemotherapy Followed by Natural Killer Cell Transplantation.
3 years after completion of therapy
Study Arms (2)
ADE
ACTIVE COMPARATORCytarabine + Daunorubicin + Etoposide NK cells for infusion are prepared using the CliniMACS System.
Clo/AraC
ACTIVE COMPARATORClofarabine + Cytarabine NK cells for infusion are prepared using the CliniMACS System.
Interventions
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Eligibility Criteria
You may qualify if:
- Age less than or equal to 21 years at time of study entry.
- No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m2 per day for one week or less ) for hyperleukocytosis.
- Written informed consent according to institutional guidelines
- Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
- Male and female participants must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
You may not qualify if:
- Down syndrome
- Acute Promyelocytic Leukemia (APL)
- Juvenile Myelomonocytic Leukemia (JMML)
- Fanconi anemia (FA)
- Kostmann syndrome
- Shwachman syndrome
- Other bone marrow failure syndromes
- Use of concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of IT therapy, hydroxyurea, or low-dose cytarabine as stated above. The patient must have recovered from all acute toxicities from any previous therapy.
- Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Pregnant or lactating patients.
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- St. Jude Children's Research Hospitallead
- Genzyme, a Sanofi Companycollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (8)
Stanford University Medical Center
Palo Alto, California, 94304, United States
Rady Children's Hospital
San Diego, California, 92123, United States
University of Chicago
Chicago, Illinois, 60637, United States
Dana Farber Cancer Institute and Children's Hospital
Boston, Massachusetts, 02215-5450, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Cook's Children's Medical Center
Fort Worth, Texas, 76104, United States
National University Health System
Singapore, 119228, Singapore
Related Publications (2)
Rubnitz JE, Lacayo NJ, Inaba H, Heym K, Ribeiro RC, Taub J, McNeer J, Degar B, Schiff D, Yeoh AE, Coustan-Smith E, Wang L, Triplett B, Raimondi SC, Klco J, Choi J, Pounds S, Pui CH. Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial. J Clin Oncol. 2019 Aug 10;37(23):2072-2081. doi: 10.1200/JCO.19.00327. Epub 2019 Jun 27.
PMID: 31246522DERIVEDNguyen R, Wu H, Pounds S, Inaba H, Ribeiro RC, Cullins D, Rooney B, Bell T, Lacayo NJ, Heym K, Degar B, Schiff D, Janssen WE, Triplett B, Pui CH, Leung W, Rubnitz JE. A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia. J Immunother Cancer. 2019 Mar 20;7(1):81. doi: 10.1186/s40425-019-0564-6.
PMID: 30894213DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jeffrey E. Rubnitz, MD, PhD
- Organization
- St. Jude Children's Research Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Jeffrey Rubnitz, MD
St. Jude Children's Research Hospital
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 20, 2008
First Posted
June 24, 2008
Study Start
August 4, 2008
Primary Completion
March 30, 2017
Study Completion
August 14, 2020
Last Updated
August 10, 2021
Results First Posted
April 2, 2018
Record last verified: 2021-07