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

Conditions

Acute Myeloid Leukemia, Advanced Malignancy, Cancer, Oncology, Oncology Patients

Keywords

AML

Brief summary

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

Shu Chin, Russ Wada, Martine Allard, Greg Slatter

Blood2019-11-133 citations

10.1182/blood-2019-131331

Concentration-QTc (C-QTc) Analysis of the MDM2 Inhibitor KRT-232 (formerly AMG 232) in Subjects with Advanced Solid Tumors, Multiple Myeloma, or Acute Myeloid Leukemia

Adekemi Taylor, Martine Allard, Cecile Kresja, Dana Lee, Greg Slatter

Blood2019-11-131 citations

10.1182/blood-2019-131481

Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia

Harry P. Erba, Pamela S. Becker, Paul J. Shami, Michael R. Grunwald, Donna Flesher et al. (10 authors)

Blood Advances2019-06-2895 citations

10.1182/bloodadvances.2019030916

Dose escalation results of a phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in patients (Pts) with relapsed/refractory (r/r) acute myeloid leukemia (AML).

Harry P. Erba, Pamela S. Becker, Paul J. Shami, Michael R. Grunwald, Donna Flesher et al. (9 authors)

Journal of Clinical Oncology2017-05-207 citations

10.1200/jco.2017.35.15_suppl.7027

Interventions

DRUGAMG 232

Given an an oral tablet in escalating doses.

DRUGTrametinib

Trametinib is an oral tablet given in a fixed dose.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Treatment Response	36 months	Complete response (CR), complete response with incomplete recovery (CRi), and duration response.

Countries

United States

Outcome results

None listed