MDACC Study Summary 2010-0570LEUKEMIA

Study Summary
No. 2010-0570LEUKEMIA:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2010-0570LEUKEMIA

Study Title:	Expanded Access Program of Ponatinib (AP24534) for Patients with Refractory Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia

Physician

New Patient Referral



Name:	Jorge Cortes	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:	713-794-5783 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Ariad Pharmaceuticals, Inc.

Phase of Study:	Phase II	Return Visit:

Treatment Agents:	Ponatinib	Home Care:

Treatment Loc:	Both at MDACC & and Other Sites

Estimated Length of Stay in Houston:

Description/
Intervention:

This is a multicenter expanded access program of oral ponatinib in patients
with CML and Ph+ ALL who have not responded to other treatments. A minimal
amount of data will be collected to check the safety of treatment with
ponatinib.

The goal of this program is to provide you the opportunity to receive access to
the investigational drug ponatinib.

Ponatinib is designed to interfere with proteins in cancer cells that may cause
different blood cancers. It is also designed to interfere with a certain
genetic mutation, called the T315I mutation, that many patients with leukemia
have. Blocking these proteins and/or this mutation may cause the cancer to
stop growing.

Study Objectives / Outcomes

The primary objective of this study is to provide ponatinib to patients with refractory CML or Ph+ ALL who are either:

Resistant or intolerant to prior approved TKIs,

Or:

Have the T315I mutation,

And:

Therapy is requested by the investigator.

Study Status Information



Study Activation / Registration Date:	05/07/2012

IRB Review and Approval Date:	05/07/2012

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	300

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) Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL.

2) For CP-CML and AP-CML be previously treated with and resistant or intolerant to imatinib, dasatinib and nilotinib or develop the T315I mutation after any TKI therapy. (A) Resistance is defined for CP-CML patients (CP at the time of initiation of TKI therapy) as follows. Patients must meet at least 1 criterion. Three months after the initiation of therapy: No cytogenetic response (>95% Ph+) or failure to achieve CHR; Six months after the initiation of therapy: Less than a minor cytogenetic response (>65% Ph+); Twelve months after the initiation of therapy: Less than a PCyR (>35% Ph+); At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of CCyR; At any time after the initiation of therapy, the development of new clonal evolution in the absence of CCyR;

3) **Continued from above: At any time after the initiation of therapy, the loss of any cytogenetic response [from complete (0%), partial (1% to 35%), minor (36% to 65%), or minimal (66% to 95%) to a response at least 1 grade worse], confirmed in at least 2 consecutive analyses separated by at least 4 weeks; At any time after the initiation of therapy, progression of disease (to AP or BP).

4) **Continued from above: (B) Resistance is defined for AP-CML patients (AP at the time of initiation of TKI therapy) as follows. Patients must meet at least 1 criterion. Three months after the initiation of therapy: failure to achieve a MaHR; At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 4 weeks; At any time after the initiation of therapy, the development of new BCRABL kinase domain mutations in the absence of a MaHR.

5) **Continued from above: (C) Intolerance is defined as: Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) in the absence of a CCyR for CP-CML patients or MaHR for AP-CML patients; Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer (400 mg daily [QD] for imatinib; 80 mg QD for dasatinib; 400 mg QD for nilotinib) in the absence of a CCyR for CP-CML patients or MaHR for AP-CML patients.

6) For BP-CML and Ph+ ALL be previously treated with and resistant or intolerant to imatinib and dasatinib or develop the T315I mutation after any TKI therapy. (A) Resistance is defined for BP-CML patients (BP at the time of initiation of imatinib or dasatinib therapy) and Ph+ ALL patients as follows. Patients must meet at least 1 criterion. One month after the initiation of therapy: failure to achieve a MaHR; At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 1 week; At any time after the initiation of therapy, the development of new BCRABL kinase domain mutations in the absence of a MaHR.

7) **Continued from above: (B) Intolerance is defined as: Non- hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) in the absence of a MaHR for BP-CML/Ph+ ALL patients; Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer (400 mg QD for imatinib; 80 mg QD for dasatinib) in the absence of a MaHR for BP-CML/Ph+ ALL patients.

8) Patients must be >/=18 years old.

9) Provide written informed consent.

10) Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

11) Men and women of childbearing potential must agree to effective contraception from the time of signing informed consent through the Follow-up Visit, approximately 30 days after last dose of ponatinib.

Exclusion Criteria:

1) Are eligible for an ongoing and accessible clinical trial of ponatinib.

2) Have not adequately recovered from AEs due to agents previously administered.

3) Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.

4) Have previously been treated with ponatinib.

5) Have significant or active cardiovascular disease, specifically including, but not restricted to: a. Myocardial infarction within 3 months prior to first dose of ponatinib, b. History of clinically significant atrial arrhythmia or any ventricular arrhythmia, c. Unstable angina within 3 months prior to first dose of ponatinib, d. Congestive heart failure within 3 months prior to first dose of ponatinib.

6) Have abnormal QTcF (>450 ms for males or >470 ms for females).

7) Have a significant bleeding disorder unrelated to CML or Ph+ ALL.

8) Have a history of pancreatitis or alcohol abuse.

9) Have elevated amylase or lipase (> 1.5 x ULN for institution) at entry.

10) Have inadequate hepatic function or any of the following: a. Total bilirubin > 1.5 x ULN for institution at entry; b. Alanine aminotransferase and aspartate aminotransferase > 2.5 x ULN for institution at entry; c. Prothrombin time >1.5 x ULN for institution at entry.

11) Have inadequate renal function or serum creatinine >2.5 x ULN for institution at entry.

12) Have uncontrolled hypertriglyceridemia or triglycerides >450 mg/dL at entry.

13) Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.

14) Women who are pregnant or lactating.

15) Underwent major surgery within 14 days prior to the first dose of ponatinib.

16) Have ongoing or active infection (including known history of human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]).

17) Suffer from any condition or illness that, in the opinion of the Investigator would compromise patient safety or interfere with the evaluation of the safety of the study drug.

Links

Registration Number: NCT01592136
Study Information on Clinical Trials Registry (clinicaltrials.gov)