MDACC Study Summary 2006-0278 (Archived)

Study Summary
No. 2006-0278:.......Leukemia......Hagop Kantarjian......Leukemia

Study Summary Title



Study Summary Number:	2006-0278

Study Title:	A Phase I, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of INNO-406 in Adult Patients with Imatinib-resistant or intolerant Philadelphia Chromosome-positive (Ph+) Leukemias

Physician

New Patient Referral



Name:	Hagop Kantarjian	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:	713-792-7026 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Weekly through cycle 1, then end of cycles 2 and 3, then every 3 months.

Treatment Agents:	INNO-406	Home Care:	Self medicated

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to find the highest tolerable dose of INNO-406 that can be given to patients with CML or ALL. The safety and effectiveness of the drug will also be studied.

Study Objectives / Outcomes

Primary Objectives
(1) To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of INNO-406 when administered as a single agent to adult patients with imatinib-resistant or intolerant Ph+ leukemias.
(2) To determine the safety profile (including acute and chronic toxicities) and tolerability of INNO-406 in this patient population.

Secondary Objectives
(1) To determine the pharmacokinetic (PK) profile of INNO-406.
(2) To assess BCR-ABL transcript levels and to analyze the BCR-ABL mutations.
(3) To assess leukemia response rates in this patient population.

Study Status Information



Study Activation / Registration Date:	07/03/2006

IRB Review and Approval Date:	06/07/2006

Study Type:	Phase I

Recruitment Status:	Terminated

Projected Accrual:	100

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) Have a confirmed diagnosis of Ph+ ALL or CML in chronic, accelerated or blastic phases that are either resistant to or intolerant of imatinib therapy.

2) Cont from #1: (1) Resistant disease is defined as either hematological (white cell count >/= 15,000 cells per mm^3 documented on two occasions separated by at least one week) or cytogenetic (> 35% of cells that are positive for the Ph chromosome in the bone marrow, as determined by G-banding in at least 20 cells in metaphase per sample, after one year of therapy; or, an absolute rise in the percentage of cells that are positive for the Ph chromosome in the bone marrow, as determined by G-banding in at least 20 cells in metaphase per sample, by 30% over best response).

3) Cont from #2: These definitions should be met in patients previously treated with >/=400 mg or the maximum tolerated dose of imatinib for CML in chronic phase patients (CML-CP); or >/=600 mg given as a single agent, or >400 mg if given in combination with chemotherapy or other agents, or the maximum tolerated dose of imatinib for CML in accelerated (CML-AP) and blast (CML-BP) phases.

4) Cont from # 3: (2) Intolerance is defined as the presence of any toxicity that prevents patients from receiving therapy (e.g. CTCAE grade 3 or 4 toxicity or persistent grade 2 toxicity).

5) Cont from #4: (3) Ph+ CML in chronic phase (CML-CP) is defined as never in blastic phase or accelerated phase before starting treatment and the presence of the following criteria (Note: Pts in second chronic phase may be enrolled, but will be analyzed as separate patient group.): (a) <15% blasts in peripheral blood & bone marrow, (b) <30% blasts plus promyelocytes in peripheral blood and bone marrow, (c) <20% basophils in the peripheral blood, (d) Platelet count of >/=100 � 10^9/L (>/=100,000/mm^3), (e) No evidence of extramedullary leukemic involvement, with the exception of liver or spleen.

6) Cont from #5: (4) Ph+ CML in accelerated phase (CML-AP) is defined as never in blastic phase prior to starting treatment, with one or more of the following criteria present within 4 weeks prior to starting treatment: a) >/= 15% but <30% blasts in blood or bone marrow; b) >/=30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that <30% blasts present in bone marrow); c) >/=20% basophils in the peripheral blood; d) Thrombocytopenia (platelets <100 x 10^9/L) unrelated to therapy;

7) Cont from #6: e) Cytogenetic clonal evolution (defined as the presence of additional chromosomal abnormalities in addition to the Philadelphia chromosome present in the same cells)

8) Cont from # 7: (5) Ph+ CML in blastic phase (CML-BP) is defined as >/=30% blasts in peripheral blood or bone marrow, or the presence of extramedullary disease other than liver or spleen.

9) Be able to provide written informed consent at study enrollment into the study.

10) Be >/=18 years old.

11) Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of </=2.

12) Have an estimated life expectancy of >/=12 weeks.

13) Be male or non-pregnant, non-lactating females. For US patients who are fertile, they must agree to use one effective barrier method of contraception (e.g. latex condom, diaphragm, or cervical cap) while on therapy and for 90 days following discontinuation of study drug. For German patients who are fertile, they must agree to use two forms of barrier method contraception (e.g. latex condom AND a diaphragm or cervical cap) while on therapy and for 90 days following discontinuation of study drug.

14) A non-fertile female is defined as: Postmenopausal (amenorrheic for ≥12 months); Undergone a complete oophorectomy or hysterectomy.

15) Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential).

16) Have adequate organ function as indicated by the following laboratory values obtained within 7 days prior to the first dose of study drug. Hepatic: Serum bilirubin </=1.5 x ULN without leukemic involvement (</= 3.0 x ULN with leukemic involvment), AST and/or ALT </=2.5 x ULN (</= 5.0 x ULN with leukemic involvement), Alkaline phosphatase </= 2.5 x ULN unless due to leukemic involvement. Renal: Serum creatinine </=1.5 x ULN or 24h creatinine Cl >/=50 mL/min (patients with a serum creatinine > 1.5 ULN will be eligible if the 24 hour creatinine clearance is >/= 50 ml/min.

Exclusion Criteria:

1) Have received chemotherapy </=1 week from the start of therapy, with the following exceptions: a) Hydroxyurea is permitted as clinically indicated before and during the first 21 days of treatment. Hydroxyurea may be permitted after the first 21 days of treatment with written approval of the Innovive Medical Monitor. b) Corticosteroids allowed up to 48 hours prior to first administration of INNO-406 (with the exception of premedication and topical/nasal steroid use which are allowed at any time).

2) Have received imatinib </=3 days prior to enrollment or who have not recovered from side effects of imatinib therapy.

3) Have impaired cardiac function, including any one of the following: Myocardial infarction within 3 months. Unstable angina pectoris. Congenital or familial long QT syndrome. Clinically significant resting bradycardia (<50 beats per minute). LVEF <45% as determined by MUGA scan or echocardiogram. Complete left bundle branch block. Right bundle branch block plus left anterior hemiblock, bifascicular block. ST depression of >1 mm in 2 or more leads and/or T wave inversion in 2 or more contiguous leads. Presence of clinically significant ventricular or atrial tachyarrhythmias.

4) Cont from #4: QTc >470 ms on screening 12-lead ECG (using Bazett's correction of QT interval formula [QTcB]). Other clinically significant heart disease (e.g. uncontrolled congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with antihypertensive medication). NYHA or CCS Class III or IV. Hypokalaemia.

5) Have an active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant at the time of treatment.

6) Have clinically significant acute or chronic liver or renal disease considered unrelated to tumor.

7) Have impaired gastrointestinal function that may significantly alter drug absorption (e.g. uncontrolled vomiting, ulcerative colitis, malabsorption, or small bowel resection).

8) Are pregnant or lactating.

9) Have psychiatric disorder(s) that would interfere with consent, study participation or follow-up.

10) Have not recovered from acute toxicity of all previous therapy prior to enrollment.

11) Have any other severe concurrent disease and/or uncontrolled medical conditions, which, in the judgment of the investigator, could predispose patients to unacceptable safety risks or compromise compliance with the protocol.

12) Have a history of another primary malignancy that is currently clinically significant or requires active intervention.

13) Are unwilling or unable to comply with the protocol.

Links

Registration Number: NCT00352677
Study Information on Clinical Trials Registry (clinicaltrials.gov)