A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia

Sponsor

Kartos Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02016729

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

7.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Open-label, sequential dose escalation and expansion study of AMG 232 in subjects with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancy Cancer Oncology Oncology Patients Acute Myeloid Leukemia	Drug: AMG 232 Drug: Trametinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 232 Alone and in Combination With Trametinib in Adult Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Actual Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Apr 19, 2017

Actual Study Completion Date :

Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 232 AMG 232 is an anti-cancer agent	Drug: AMG 232 Given an an oral tablet in escalating doses. Drug: Trametinib Trametinib is an oral tablet given in a fixed dose.
Experimental: AMG 232 & Trametinib AMG 232 and Trametinib are anti cancer agents	Drug: Trametinib Trametinib is an oral tablet given in a fixed dose.

Arm

Intervention/Treatment

Experimental: AMG 232

AMG 232 is an anti-cancer agent

Drug: AMG 232

Given an an oral tablet in escalating doses.

Drug: Trametinib

Trametinib is an oral tablet given in a fixed dose.

Experimental: AMG 232 & Trametinib

AMG 232 and Trametinib are anti cancer agents

Drug: Trametinib

Trametinib is an oral tablet given in a fixed dose.

Outcome Measures

Primary Outcome Measures

To evaluate the safety and tolerability of AMG 232 [36 months]
To evaluate the safety and tolerability of AMG 232 by reviewing clinically significant or ≥ Grade 3 changes in safety laboratory tests, physical examinations, ECGs, or vitals signs in all subjects enrolled.
Characterize the pharmacokinetics of AMG 232 alone and in combination with trametinib when administered orally. [36 months]
PK parameters will include, but are not limited to, area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax).
Determine the maximum tolerated dose of AMG 232 alone and in combination with trametinib, if possible. [36 months]
The MTD is defined at the highest dose level with an observed incidence of dose limiting toxicity in < 33% of subjects enrolled in a cohort.

Secondary Outcome Measures

Treatment Response [36 months]
Complete response (CR), complete response with incomplete recovery (CRi), and duration response.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women > 18 years old
Pathologically-documented, definitively-diagnosed AML that is relapsed or refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy
Ability to take oral medications and willing to record daily adherance to investigational product
Adequate hematological, renal, hepatic, and coagulation laboratory assessments

Exclusion Criteria:

Active infection requiring intravenous (IV) antibiotics
Prior participation in an investigational study (procedure or device) within 21 days of study day 1
Major surgery within 28 days of study day 1
Anti-tumor therapy within 14 days of study day 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35294
2	Research Site	Buffalo	New York	United States	14263
3	Research Site	Charlotte	North Carolina	United States	28204
4	Research Site	Salt Lake City	Utah	United States	84112
5	Research Site	Seattle	Washington	United States	98101