An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)

Kartos Therapeutics

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)

Relapsed or Refractory Acute Myeloid Leukemia (AML)

Treatments

Drug: KRT-232

Drug: Cytarabine

Drug: Decitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT04113616

KRT-232-104

Details and patient eligibility

About

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, when administered alone and in combination with low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be relapsed/refractory (having failed prior therapy) and will be assigned to receive monotherapy (KRT-232 alone) or combination therapy (KRT-232 with LDAC or KRT-232 with Decitabine).

Enrollment

70 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Part A: Patients with relapsed or refractory AML, or newly-diagnosed AML secondary to MPN
Part B:Patients with relapsed or refractory AML secondary to MPN (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]); patients may have been treated with ≥1 prior lines of therapy for their AML secondary to MPN.
Adequate hepatic and renal function
Appropriate prior treatment with an FLT3 or IDH1/2 inhibitor where applicable

Key Exclusion Criteria:

Patients who are TP53 mutation positive
Prior treatment with an MDM2 antagonist therapy
Patients treated with ≥ 18 g/m2 of cytarabine within the prior 90 days are not eligible to be treated with cytarabine on this study but may be treated with decitabine (for Part A) .
Patients previously treated with decitabine are not eligible to receive decitabine on this study but may be treated with cytarabine (for Part A) .
Patients who have received an allogeneic HSCT within 90 days of enrollment or who have active graft-versus-host disease requiring active therapy (for Part A)
Allogeneic stem cell transplant within 3 months; autologous stem cell transplant within 3 months or active graft-versus-host disease prior to first dose of study treatment (for Part B)
Patients who have received immunosuppressive therapy for graft-versus-host disease within 1 month prior to enrollment into this study
Patients who are eligible for an allogeneic HSCT per the opinion of the investigator and have a donor. Patients who are HSCT-eligible in the opinion of the investigator, but who refuse a transplant, are eligible for the study.
Patients with known CNS involvement with AML, acute promyelocytic leukemia (APL), or a history of bleeding diathesis
Patients who have had major surgery within 28 days prior to the first treatment with KRT-232
Women who are pregnant or breastfeeding

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

70 participants in 6 patient groups

Part A - Arm 1

Experimental group

Description:

KRT-232+LDAC: KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with LDAC administered at 20 mg/m2/day subcutaneously on Days 1-10 in a 28-day cycle.

Treatment:

Drug: Cytarabine

Drug: KRT-232

Part A - Arm 2

Experimental group

Description:

KRT-232(7-Day)+Decitabine: KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.

Treatment:

Drug: Decitabine

Drug: KRT-232

Part A - Arm 3

Experimental group

Description:

KRT-232(14-Day)+Decitabine: KRT-232 will be administered orally, once daily (QD), on Days 1-7 and Days 15-21 (7 days on/7 days off/7 days on/7 days off) in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.

Treatment:

Drug: Decitabine

Drug: KRT-232

Part B - Arm 1

Experimental group

Description:

KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle

Treatment:

Drug: KRT-232

Part B - Arm 2

Experimental group

Description:

KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle in Cycle 1, followed by 240 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day cycle, in the subsequent cycles.

Treatment:

Drug: KRT-232

Part B - Arm 3

Experimental group

Description:

KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle.

Treatment:

Drug: KRT-232