MDACC Study Summary 2006-1096 (Archived)

Study Summary
No. 2006-1096:.......Leukemia......Jean-Pierre Issa......Leukemia

Study Summary Title



Study Summary Number:	2006-1096

Study Title:	A Phase I Clinical Trial of Vorinostat in Combination with Decitabine in Patients with Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Physician

New Patient Referral



Name:	Jean-Pierre Issa	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-745-2260 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Merck

Phase of Study:	Phase I	Return Visit:	At least weekly.

Treatment Agents:	Decitabine Vorinostat	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to find the highest dose of vorinostat, given in combination with decitabine, that can be given to help to control AML or MDS. The safety of both study drugs will also be studied.

Study Objectives / Outcomes

1) To determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of vorinostat administered once daily for 7 to 14 days in a 28-day cycle concurrently and sequentially with decitabine in patients with AML or intermediate to high risk MDS. Hypothesis: The incidence of dose limiting toxicities (DLTs) when vorinostat is administered for 14 out of 28 days in combination with 5 days of IV decitabine 20 mg/m² in a 28-day cycle at MTD will be less than 33%. (2) To evaluate the safety and tolerability of vorinostat in combination with decitabine, including qualitative, quantitative, and dose-limiting adverse effects. Hypothesis: Administration of vorinostat in combination with decitabine to patients with intermediate to high risk MDS or AML is sufficiently safe and well tolerated to permit further study. (3) To evaluate the in vivo molecular and biological effects of vorinostat in patients with intermediate to high risk MDS as defined by IPSS, refractory or relapsed AML, or previously untreated AML patients (if not candidates for standard cytotoxic chemotherapy) through analysis of histone modification, DNA methylation and gene and protein expression.

Exploratory objectives:
1) To determine the clinical activity of vorinostat in combination with decitabine in patients with refractory or relapsed AML; or intermediate to high risk MDS as defined by IPSS, or previously untreated AML patients (if not candidates for standard cytotoxic chemotherapy).

Study Status Information



Study Activation / Registration Date:	05/18/2007

IRB Review and Approval Date:	03/25/2007

Study Type:	Phase I

Recruitment Status:	Terminated

Projected Accrual:	80

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patient has an established diagnosis of one of the following: Intermediate-high risk MDS as defined by IPSS (both intermediate-1 and intermediate-2 are eligible); Refractory or relapsed AML; Untreated AML (if patient is not a candidate for standard cytotoxic chemotherapy).

2) Patient age is > or = 18 years; for untreated AML cohort, age > or = 60 years

3) Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2.

4) Patient is at least 4 weeks from any prior chemotherapy except hydroxyurea, biological therapy, major surgery, or any investigational therapy and has adequately recovered from the toxicities and/or complications of prior therapy unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first 2 weeks of therapy.

5) Patient has adequate liver function with total bilirubin < 2 mg/dL and ALT < 3 x ULN.

6) Patient has adequate renal function with serum creatinine < 2 mg/dL or creatinine clearance > or = 60 ml/min for patients with creatinine levels > or = 2 mg/dL.

7) Patient is known to not be refractory to platelet transfusions.

8) Female patient of childbearing potential has a negative serum pregnancy test (beta-hCG) within 72 hours prior to receiving the first dose of vorinostat and or decitabine. Female patient is not actively breastfeeding at the time of study entry.

9) Female patient is either post-menopausal, free from menses for > 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with visit 1.

10) Male patient agrees to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving decitabine and for 2 months post study.

11) Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.

12) Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.

13) Patient is able to swallow capsules.

Exclusion Criteria:

1) Patient had prior treatment with an HDAC inhibitor (e.g., depsipeptide or NSC-630176, MS-275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781, valproic acid, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.

2) Patient has a known prior use of decitabine (DACOGEN) or azacitidine (VIDAZA) therapy.

3) Patient has active or uncontrolled infection and is taking antibiotics for reasons other than prophylaxis.

4) Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.

5) Patient is unable to take and/or tolerate oral medications on a continuous basis.

6) Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy.

7) Patient has a known history of active hepatitis B or hepatitis C infection.

8) Patient has a known allergy or hypersensitivity to any component of vorinostat or decitabine.

9) Patient with a "currently active" second malignancy, other than nonmelanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.

Links

Registration Number: NCT00479232
Study Information on Clinical Trials Registry (clinicaltrials.gov)