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Vorinostat Combined With Gemtuzumab Ozogamicin, Idarubicin and Cytarabine in Acute Myeloid Leukemia

NCT01039363 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 27

Last updated 2009-12-25

No results posted yet for this study

Summary

The prognosis of elderly patients with relapsed or refractory acute myeloid leukemia (AML) is grave. Because of their chronological age and/or the presence of multiple co-morbidities, treatment-related mortality in elderly patients with AML is quite high although higher intensive treatment is mandatory to overcome chemoresistant characteristic of their disease. Several regimens have been evaluated as salvage chemotherapy for relapsed or refractory AML such as Mitoxantrone/High dose Cytarabine or Amsacrine/High dose Cytarabine. These regimens could achieve complete remission (CR) in a part of patients, but resulted in higher treatment related mortality (TRM). Accordingly, less intensive salvage regimen is needed for elderly patients with relapsed or refractory AML.

The activity of histone deacetylase (HDAC) inhibitor, Vorinostat or Suberoylanilide hydroxamic acid (SAHA), against AML has been suggested in cell line models and in animal model as well as in a phase 1 trial. The phase 1 study determined the MTD of oral Vorinostat as 200mg twice daily or 250mg thrice daily. In addition, the phase 1 trial showed the antitumor activity of Vorinostat with 17% of response rate in patients with advanced leukemia or myelodysplastic syndrome (MDS). Accordingly, further study is recommended to demonstrate the clinical activity of Vorinostat in AML.

In terms of the combining drug with Vorinostat, anthracycline is one of the best candidate. A in vitro study demonstrated that the combination of anthracycline (esp. idarubicin) with HDAC inhibitor have significant clinical activity against leukemia. Another candidate is Gemtuzumab ozogamicin, which is a calicheamicin-conjugated antibody directed against CD33 antigen on AML blasts. The U.S. FDA also approved the use of GO in relapsed AML as a monotherapy. A study also showed that the combinational therapy of GO with attenuated doses of standard induction chemotherapy could successfully induce CR without increasing treatment-related mortality in AML patients aged 55 or older. A in vitro study reported that HDAC inhibitor valproic acid augmented the clinical activity of GO toward CD33+ AML cells. The study demonstrated that the strategy using HDAC inhibitor together with GO could potentially induce synergistic proapoptotic activity against AML blasts without increasing toxicity. In our center, so far we treated relapsed or refractory AML patients using the salvage regimen including GO (3mg/m2/dayx1day) plus attenuated Idarubicin/Cytarabine (Idarubicin 12mg/m2/day for 2 days and intermediate dose Cytarabine). So far, the CR rate from the regimen is around 50% without increasing TRM. Accordingly, we will determine the efficacy and toxicity of Vorinostat-incorporating salvage regimen based on the GO+IA chemotherapy in patients 50 years old or older with relapsed or refractory AML.

Conditions

Interventions

DRUG

Salvage reinduction chemotherapy including Gemtuzumab ozogamicin, Idarubicin and Cytarabine and Vorinostat

Salvage reinduction therapy: Vorinostat 200mg BID po (D1-14) Gemtuzumab ozogamicin 3 mg/m2 once (D1) Idarubicin 12mg/m2 for 2 days (D2-3) Cytarabine 500mg/m2 bid IV for 5 days (D2-6) Maintenance: Once achieved CR, then Vorinostat 200mg BID po for 2 weeks, then 1 week's rest (1 cycle) for 11 cycles * Vorinostat should be stopped at least 2 weeks ahead of starting of consolidation therapy. * Gemtuzumab will be omitted in a consolidation schedule. * Allogeneic hematopoietic stem cell transplantation (HSCT) can be performed if HLA-matched sibling or unrelated donor is available. Vorinostat will be stopped 2 weeks prior to starting of conditioning regimen for allogeneic HSCT.

Sponsors & Collaborators

  • Samsung Medical Center

    lead OTHER

Principal Investigators

  • Dong Hwan Kim, M.D.,Ph.D. · Division of Hematology and Oncology/Samsung Medical Center

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
50 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Countries

  • South Korea

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01039363 on ClinicalTrials.gov