Clinical trial NCT00818649
Conditions: Leukemia Myelodysplastic Syndrome
Keywords: de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes refractory anemia with excess blasts adult acute myeloblastic leukemia with maturation (M2) adult acute myeloblastic leukemia without maturation (M1) adult acute minimally differentiated myeloid leukemia (M0) adult acute myelomonocytic leukemia (M4) adult acute monoblastic leukemia (M5a) adult acute monocytic leukemia (M5b) adult erythroleukemia (M6a) adult pure erythroid leukemia (M6b) adult acute megakaryoblastic leukemia (M7) recurrent adult acute myeloid leukemia untreated adult acute myeloid leukemia 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)
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2009-01-01; Completion date: 2012-05-01
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.

Detailed description:
OBJECTIVES:

Primary

* To determine the clinical response to bortezomib and vorinostat in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia, as defined by the International Working Group response criteria.

Secondary

* To characterize the quantitative and qualitative toxicities of this regimen in these patients.
* To assess the effect of this regimen on natural killer (NK) cell function, in terms of activating and inhibitory receptor alterations, target cell ligand and HLA class I modulation, and NK-mediated cell killing.
* To correlate the above changes with clinical response.

OUTLINE: Patients receive bortezomib subcutaneously (SQ) on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response, partial response, or hematologic improvement may receive 3 additional courses of therapy (for a maximum of 6 courses).

Bone marrow and peripheral blood samples are collected at baseline and at the completion of 3 courses of therapy for analysis of target cells (myeloid blasts) (i.e., HLA class I receptor analysis and natural killer \[NK\] cell receptor ligand analysis) and analysis of activating NK cell receptor alterations and NK-mediated cell killing.

After completion of study treatment, patients are followed periodically for up to 1 year.

Arms: arm 1: This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles.
Interventions: intervention 1: bortezomib intervention 2: vorinostat
Intervention descriptions: intervention 1: 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle intervention 2: 400 mg orally (po) every day on days 1-14 of a 21 day cycle

Protocol documents: