MDACC Study Summary 2012-0569

Study Summary
No. 2012-0569:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2012-0569

Study Title:	A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3 Activating Mutations

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:	AROG Pharmaceuticals, LLC

Phase of Study:	Phase II	Return Visit:

Treatment Agents:	Crenolanib	Home Care:

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:


Description/ Intervention:	The goal of this clinical research study is to learn if crenolanib can help to control FLT3 mutated AML that has gotten worse. Crenolanib is designed to block the FLT3 gene mutation, which may kill the leukemia cells.

Study Objectives / Outcomes

Primary Objectives:

To determine the response rate to crenolanib, including the rates of complete remission (CR), CR with incomplete blood count recovery (CRi), and partial remission (PR), in relapsed/refractory AML patients with FLT3 activating mutations after first cycle (28-days)
To determine the safety and tolerability of crenolanib in AML patients with FLT3 activating mutations

Secondary Objectives:

To determine the duration of response in AML patients with activating FLT3 mutations treated with crenolanib
To determine the progression free survival and overall survival of AML patients with activating FLT3 mutations treated with crenolanib
To characterize crenolanib pharmacokinetics in adult patients with AML and relate crenolanib exposure to outcome (e.g., toxicity and/or FLT3 inhibition)
To analyze phospho-FLT3 and other pharmacodynamic markers from serially collected circulating leukemic blasts and/or marrow blast samples

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	10/05/2012

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	41

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) Relapsed/refractory patients with primary AML with FLT3-ITD and/or other FLT3 activating mutations, whose leukemia has recurred after prior chemotherapy but never received a FLT3 inhibitor (Cohort A) or whose leukemia has progressed after prior therapy and have history of prior exposure to one or more FLT3 TKIs (Cohort B).

2) Patients must have tested positive for FLT3-ITD and/or other FLT3 activating mutations.

3) Males and females age >/=18 years.

4) ECOG PS 0-2.

5) Adequate liver function, defined as bilirubin </=1.5x ULN, ALT </=3.0x ULN, and AST </=3.0x ULN.

6) Adequate renal function, defined as serum creatinine </=1.5x ULN.

7) Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia).

8) In the absence of rapidly progressing leukemia, subjects should have received no anti-leukemic therapy (except hydroxyurea) for 2 weeks (for classical cytotoxic agents and FLT3 inhibitors) prior to first dose of crenolanib.

9) Negative pregnancy test for women of childbearing potential (WOCBP). WOCBP must practice contraception. Acceptable methods of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and abstention. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use effective contraceptive methods, as described above, during the study. Women considered not of childbearing potential include any of the following: no menses for at least 5 years or menses within 5 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation.

10) Able and willing to provide written informed consent.

Exclusion Criteria:

1) Absence of a FLT3 activating mutation.

2) Secondary AML or AML in the setting of antecedent hematological disorders.

3) <5% blasts in blood or marrow at screening.

4) Concurrent chemotherapy, systemic immuno-suppressants, or targeted anti-cancer agents, other than hydroxyurea.

5) Patients with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy.

6) HIV infection or active hepatitis B or C.

7) Known clinically active central nervous system (CNS) leukemia.

8) Patients who have had HSCT and are within 180 days of an allogeneic transplant or 90 days of an autologous transplant, and/or have received immunosuppressive drugs for management or prophylaxis of GVHD within 30 days of enrollment, and/or have clinically significant graft-versus-host disease requiring treatment, and/or have >Grade 1 persistent non hematological toxicity related to the transplant.

9) Major surgical procedures within 14 days of Day 1 administration of crenolanib.

10) Unwillingness or inability to comply with protocol.

Links

Registration Number: NCT01522469
Study Information on Clinical Trials Registry (clinicaltrials.gov)