NCT00895934

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

A Phase 1/2 Study of Vorinostat (Zolinza®) in Combination With Gemtuzumab Ozogamicin (Mylotarg®) and Azacitidine (Vidaza®) in Patients 50 Years of Age and Older With Relapsed/Refractory Non-APL Acute Myeloid Leukemia (AML)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

Detailed description

PRIMARY OBJECTIVES: I. Determine the vorinostat dose with the most favorable efficacy and toxicity when combined with azacitidine and GO. SECONDARY OBJECTIVES: I. Describe the complete response (CR)/ CR with inadequate recovery (CRi) rate after a total of 6 cycles of therapy. II. Describe the disease-free survival of patients that achieve CR/CRi. III. Determine whether acute myeloid leukemia (AML) characteristics associated with preclinical GO efficacy predict for clinical benefit, and assess whether differentiation-inducing agents modulate these characteristics and lower the apoptotic threshold for calicheamicin-gamma1-induced cytotoxicity (in vitro correlative and mechanistic studies). OUTLINE: This is phase I, dose-escalation study of vorinostat followed by a phase II study. Patients receive vorinostat orally (PO) on days 1-9, azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4 and 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years.

Conditions

• Adult Acute Megakaryoblastic Leukemia (M7)
• Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
• Adult Acute Monoblastic Leukemia (M5a)
• Adult Acute Monocytic Leukemia (M5b)
• Adult Acute Myeloblastic Leukemia With Maturation (M2)
• Adult Acute Myeloblastic Leukemia Without Maturation (M1)
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Adult Acute Myelomonocytic Leukemia (M4)
• Adult Erythroleukemia (M6a)
• Adult Pure Erythroid Leukemia (M6b)
• Recurrent Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	vorinostat	Given orally
DRUG	gemtuzumab ozogamicin	Given intravenously (IV)
DRUG	azacitidine	Given IV or subcutaneously (SC)

Timeline

• Start date: 2009-05-01
• Primary completion: 2013-07-01
• Completion: 2013-09-01
• First posted: 2009-05-08
• Last updated: 2019-05-23
• Results posted: 2015-02-06

Locations

4 sites across 1 country: United States