AML08: Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Study Of NK Cell Transplantation In Newly Diagnosed Acute Myeloid Leukemia

A Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy and of Natural Killer Cell Transplantation Versus Conventional Consolidation Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

Categories:

Leukemia / Lymphoma

Bone Marrow Transplant

Diseases Treated:

Acute myeloid leukemia (AML)

Eligibility Overview:

  • 21 years of age or younger at the time of study entry
  • No prior therapy for AML except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine for hyperleukocytosis
  • Must not have Down syndrome, acute promyelocytic leukemia (APL), juvenile myelomonocytic leukemia (JMML), Fanconi anemia (FA), Kostmann syndrome, Shwachman syndrome and other  bone marrow failure syndromes

Description

Although the treatment outcome for children with leukemia has improved dramatically during the past 20 years, the cure rate for acute myeloid leukemia (AML) continues to lag behind that achieved for children with acute lymphoblastic leukemia (ALL). Most patients with AML achieve remission after 1 to 2 courses of induction therapy, but approximately half of these patients suffer relapse of their disease. The overall goal of our AML program is to develop novel therapies that overcome drug resistance, decrease relapse rates, and reduce the short- and long-term adverse effects of treatment.

NK cells are a type of toxic white blood cell that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. They kill cells by releasing small granules of proteins called perforin and granzyme that cause the target cell to die. The usage of NK cells provide lot of benefits. The normal role of NK cells is to control infection and prevent cancer. In addition to the anti-leukemia effects, NK cells are capable of reducing the incidence of graft rejection and graft versus host disease (GVHD) in animal models

Numerous responses have been observed after treatment with clofarabine in heavily pre-treated relapsed/refractory patients with ALL or AML. The purpose of this study is to assess the feasibility and effectiveness of a new form of therapy, haploidentical NK cell transplantation, in patients with standard risk AML. This study will also investigate the efficacy of clofarabine + cytarabine in newly diagnosed patients with AML and attempt to optimize outcome through the use of Minimal residual disease (MRD) adapted therapy and further improvements in supportive care.

Objectives

  • To compare the immunologic complete response rate after one course of therapy in patients who receive cytarabine + daunorubicin + etoposide (ADE) with that in patients who receive clofarabine + cytarabine
  • To estimate the event-free survival (EFS) of standard risk (SR) patients who receive chemotherapy alone and the EFS of SR patients who receive chemotherapy followed by natural killer (NK) cell transplantation
  • To genotype natural killer (NK) cell receptors and measure their expressions at diagnosis and after induction therapy, and to explore the associations of these features with treatment outcome

Eligibility

Inclusion Criteria:

  • 21 years of age or younger at the time of study entry
  • No prior therapy for AML except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine for hyperleukocytosis
  • Written informed consent according to institutional guidelines
  • Negativity pregnancy test for female patients
  • Male and female participants must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

  • Participants will not be eligible for the study if they have Down syndrome, Acute Promyelocytic Leukemia (APL), Juvenile Myelomonocytic Leukemia (JMML), Fanconi anemia (FA), Kostmann syndrome, Shwachman syndrome and 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

Jeffrey E. Rubnitz, MD, PhD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.