MDACC Study Summary 2007-0848

Study Summary
No. 2007-0848:.......Leukemia......Guillermo Garcia-Manero......Leukemia

Study Summary Title



Study Summary Number:	2007-0848

Study Title:	A Phase I Dose Escalation Study of Oral SB939 when administered Thrice Weekly (every other day) for 3 weeks in a 4-week cycle in Patients with Advanced Malignancies

Physician

New Patient Referral



Name:	Guillermo Garcia-Manero	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:	713-745-3428 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	S*BIO Pte Ltd

Phase of Study:	Phase I	Return Visit:	Three times a week for the 1st 3 weeks. Weekly thereafter.

Treatment Agents:	SB939	Home Care:	NA

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

Estimated Length of Stay in Houston:	NA

Description/
Intervention:

The goal of this clinical research study is find the highest tolerable dose of
SB939 (the drug being studied) that can be given to patients with cancer of the
blood. The safety of this drug will also be studied. Researchers want to
understand how well patients with advanced cancer cope with the side effects of
SB939 at different doses and how well they respond to the drug. They want to
find the recommended safe dose for advanced cancer patients, as well as
understand how these patients break down SB939 in their bodies.

Study Objectives / Outcomes

The investigators at M D Anderson Cancer Center will only participate in Arm B.

Primary:

To assess the safety and tolerability of SB939, administered orally every other day 3 times a week for 3 consecutive weeks, repeated every 4 weeks, in patients with advanced malignancies.

Secondary:

Establish the maximum tolerated dose (MTD) and a recommended phase II dose (RD) of SB939 as a single agent when administered every other day 3 times a week for 3 consecutive weeks, repeated every 4 weeks;
Determine the dose limiting toxicities (DLTs) of SB939;
Determine the pharmacokinetic (PK) profile of SB939;
Assess histone acetylation in PBMC and other biomarkers;
Document anti-tumor activity.

Study Status Information



Study Activation / Registration Date:	12/04/2008

IRB Review and Approval Date:	09/08/2008

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	80 (30 Arm A / 50 Arm B)

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) During dose escalation: Hematologic malignancy, including refractory or relapsing leukemia, high-risk myelodysplastic syndrome (MDS), multiple myeloma (MM), myelofibrosis (MF),indolent or aggressive non- Hodgkin's lymphoma (NHL), or Hodgkin's disease, that has failed, relapsed, or is not eligible for standard effective therapy or a peripheral blood stem cell transplant;

2) When the RD is reached: Patients with MDS that is classified as International Prognostic Scoring System (IPSS) risk category intermediate 1 or greater and that have failed at least one prior therapy or patients with refractory or relapsing AML. Patients must have failed, relapsed or not be eligible for standard effective therapy or a peripheral blood stem cell transplant.

3) During dose escalation and at the RD level, all patients must also meet the following criteria:

4) Age >/= 18 years;

5) ECOG performance status (PS) 0-2;

6) Life expectancy >/= 3 months;

7) Subjects must have adequate non-hematologic organ system function, incl the following: Hepatic: total bilirubin </=1.5 x upper limit of normal (ULN); transaminases (AST/SGOT &/or ALT/SGPT) </=2.5 x ULN (<5 x ULN if documented liver metastases); Renal: serum creatinine <160 mg/dl or calculated creatinine clearance >/=55 mL/min (Cockroft and Gault formula); Cardiac: cardiac quantitative troponin T (TnT) within normal range by the inst standard; subj who have been treated with anthracycline, or significant radiation to the chest wall, should have baseline LVEF >/= 50% prior to initiation of tx;

8) No pregnancy or breastfeeding. Female patients must be surgically sterile or postmenopausal or must agree to use effective contraception during the period of treatment. All female patients with reproductive potential must have a negative pregnancy test (serum) within 14 days prior to enrollment.

9) Male patients must be surgically sterile or must agree to use effective contraception during the period of treatment. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate;

10) No clinically significant co-morbidities, such as cardiac or pulmonary disease, active CNS disease, and active infection;

11) No known human immunodeficiency virus (HIV) infection;

12) Ability to cooperate with treatment and follow-up;

13) Ability to understand and willingness to sign informed consent prior to initiation of any study procedures.

Exclusion Criteria:

1) Failed to recover from the reversible effects of previous chemotherapy, radiotherapy, or immunotherapy prior to enrollment;

2) Any of the following in the past 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically symptomatic and uncontrolled cardiovascular disease, ongoing cardiac dysrhythmias of NCI CTC Grade >/=2, atrial fibrillation of any grade. Prolongation of the QTc interval to >450 msec for males or >470 msec for females at baseline;

3) Received any of the following within the specified time frame prior to administration of study drug: any investigational agent within 14 days or 5 half-lives, whichever is longer; previous therapy for malignancy within 21 days, including any chemotherapy, immunotherapy, biological or hormonal therapy (6 weeks for nitrosoureas or mitomycin C); hydroxyurea within 14 days; major surgery within 4 weeks;

4) Concomitant treatment with HDAC inhibitors such as valproic acid is not permitted;

5) Known brain metastasis or leptomeningeal disease;

6) Manifestation of malabsorption due to prior surgery, gastrointestinal (GI) disease, or for an unknown reason. Patients may have had major GI surgery but must not have residual symptomatic manifestations of malabsorption;

7) Any acute or chronic medical or psychiatric condition, or a laboratory abnormality that may increase the risks associated with study participation/study drug administration or may interfere with the interpretation of study results.

Links

Registration Number: NCT00741234
Study Information on Clinical Trials Registry (clinicaltrials.gov)