MDACC Study Summary 2008-0245

Study Summary
No. 2008-0245:.......Leukemia......Guillermo Garcia-Manero......Leukemia

Study Summary Title



Study Summary Number:	2008-0245

Study Title:	Phase I Study of the Histone-deacetylase Inhibitor JNJ-26481585 in Subjects with Advanced or Refractory Leukemia or Myelodysplastic Syndrome

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:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Phase of Study:	Phase I	Return Visit:	n/a

Treatment Agents:	JNJ-26481585	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:	Weekly during first course and monthly therafter.


Description/ Intervention:	The goal of this clinical research study is to find the highest tolerable dose of JNJ-26481585 that can be given to patients with advanced or refractory leukemia or MDS.

Study Objectives / Outcomes

The primary objective of the study is to determine the safety (adverse event (AE) profile, dose-limiting
toxicity and maximum tolerated dose) of JNJ-26481585.

The secondary objectives of the study are: to determine the pharmacokinetic profile of JNJ-26481585,
to explore the pharmacodynamic effects of JNJ 26481585 and, to explore antitumor activity of
JNJ-26481585.

Study Status Information



Study Activation / Registration Date:	02/03/2009

IRB Review and Approval Date:	02/03/2009

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	72

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) Age 18 years or older

2) Histologically or cytologically confirmed advanced or refractory AML-WHO classification, acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML) in blast phase, refractory chronic lymphocytic leukemia (CLL), MDS-WHO classification, or chronic myelomonocytic leukemia (CMML-WHO classification);

3) For subjects with ALL and AML: refractory to induction chemotherapy, or relapse after induction chemotherapy, or not amenable to standard induction therapy: Subjects with acute promyelocytic leukemia (APL) must have received prior therapy containing all-trans retinoic acid (ATRA) and arsenic trioxide unless there was a contraindication for such therapies;

4) For subjects with MDS and CMML: subjects with any IPSS are eligible. Subjects with IPSS INT-2 or high risk must have been refractory to hypomethylating agent (decitabine or azacitidine), must have relapsed after such therapy, or were intolerant to or have a contraindication to such therapy; subjects with IPSS low risk or INT-1 MDS associated with a deletion 5q cytogenetic abnormality must have received prior lenalidomide-based therapy unless the subject was intolerant to or had a contraindication for such therapy;

5) For subjects with CML in blast phase: subjects must have failed imatinib and dasatinib/nilotinib based therapy or were intolerant to such therapies;

6) For subjects with refractory CLL: subjects must be refractory to standard therapies, or relapse after standard therapies and have no other available standard treatment options;

7) For Part II of the study (MDS Expansion Phase), only subjects with MDS-WHO classification will be enrolled. These subjects must also meet the requirements for MDS subjects specified above.

8) Eastern Cooperative Oncology Group (ECOG) Performance Status Score 0, 1 or 2;

9) Left Ventricular Ejection Fraction >/= 50% as assessed by MUGA scan or echocardiography at screening;

10) Adequate liver function: total bilirubin level </= 1.5 x institutional upper limit of normal (ULN), unless due to hemolysis or Gilbert's syndrome, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 x institutional ULN;

11) Adequate renal function: serum creatinine </= 1.5 x institutional ULN;

12) Normal electrolytes at baseline and specifically serum corrected Calcium (Ca) >/= 2.2 mmol/L, Magnesium (Mg) >/= 0.8 mmol/L and Potassium (K) >/= 3.5 mmol/L.

13) Females (of child bearing potential) & male subjects (w/ a partner of child-bearing potential) must use medically acceptable methods of birth control before study entry, for duration of study & for at least 3 mos after last intake of study drug. Males must accept use of condoms when sexually active during the study. Medically acceptable methods of contraception that may be used by subject and/or his/her partner include oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method, surgical sterilization (e.g., vasectomy or tubal ligation);

14) Negative pregnancy test (urinary beta human chorionic gonadotropin [β-HCG]) at screening (applicable to women of child bearing potential who are sexually active);

15) Negative hepatitis B, C and HIV test within last 3 months;

16) Signed informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study;

17) For the pharmacogenomic component where local regulations permit, signed informed consent for correlative research indicating whether they do or do not wish to participate in the correlative research component of the study.

Exclusion Criteria:

1) Known or suspected involvement of the CNS;

2) Chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy or treatment with investigative agent within 3 weeks before study drug administration (except hydroxyurea which should be stopped at least 24 hours prior to first dose);

3) Unstable angina, or myocardial infarction within the preceding 12 months; congestive heart failure New York Heart Association (NYHA) Class II-IV (see Attachment 4); history of any of the following: sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, cardiac arrest, Mobitz II second degree heart block, or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy;

4) Continued from #3: family history of short QT syndrome, long QT syndrome,sudden unexplained death at a young age (less than/equal to 40 years), drowning or sudden infant death syndrome in a first degree relative (i.e., biological parent, sibling, or child); obligate use of a cardiac pacemaker, QTc at screening > 450 ms in males / > 470 ms in females; or any other cardiac abnormality that, in the opinion of the investigator, medical monitor, or consultant cardiologist, may place the subject at an unacceptably increased risk with study drug;

5) Receiving medications known to have a risk of causing QTc prolongation and torsades de pointes.

6) Grade >1 neuropathy at baseline;

7) Females who are pregnant or breast-feeding;

8) Subjects previously treated with an HDAC inhibitor (e.g. vorinostat, MS 275, LBH-589, depsipeptide, MGCD1003, PXD101, other) are excluded from the Part II Expansion Phase of the study;

9) Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, psychiatric illness, or social situation that may potentially impair subject's compliance with study procedures;

10) Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration);

11) Any other medical condition that in the opinion of the Investigator makes it undesirable for a patient to participate;

Links

Registration Number: NCT00676728
Study Information on Clinical Trials Registry (clinicaltrials.gov)