A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT03484520 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M16-1832017-003213-26
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 13

Brief Summary

An open-label, dose-escalation study to assess safety, pharmacokinetics and efficacy as well as determine the recommended Phase 2 doses of co-administered therapy of dinaciclib and venetoclax for patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML).

Conditions

Cancer - Acute Myeloid Leukemia

Keywords

Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib

Outcome Measures

Primary Outcomes (10)

• Tmax of Venetoclax

  Time to maximum plasma concentration (Tmax) of venetoclax.

  Approximately 29 days after first dose of study drug

• Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax

  Tthe RPTD of co-administered venetoclax and dinaciclib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.

  Minimum first cycle of dosing (21 days)

• Cmax of Venetoclax

  Maximum observed plasma concentration (Cmax) for Venetoclax.

  Approximately 29 days after first dose of study drug

• AUCt of Venetoclax

  Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt)

  Approximately 29 days after first dose of study drug

• AUC0-24 Post-dose of Venetoclax

  Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.

  Approximately 29 days after first dose of study drug

• Cmax of Dinaciclib

  Maximum plasma concentration (Cmax) of dinaciclib.

  Approximately 29 days after first dose of study drug

• Half-life (t1/2) of Dinaciclib

  Half-life (t1/2) of dinaciclib.

  Approximately 29 days after first dose of study drug

• AUCt Post-dose of Dinaciclib

  Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.

  Approximately 29 days after first dose of study drug

• AUC0-∞ of Dinaciclib

  Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.

  Approximately 29 days after first dose of study drug

• Clearance of Dinaciclib

  Clearance (CL) of dinaciclib.

  Approximately 29 days after first dose of study drug

Secondary Outcomes (3)

• Complete Response (CR) Rate

  Up to approximately 18 months

• Composite CR Rate (CR + CRi)

  Up to approximately 18 months

• Objective Response Rate (ORR)

  Up to approximately 18 months

Study Arms (1)

Venetoclax + Dinaciclib

EXPERIMENTAL

Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.

Drug: Venetoclax; Drug: Dinaciclib

Interventions

Venetoclax DRUG

tablet, oral

Also known as: ABT-199, GDC-0199

Venetoclax + Dinaciclib

Dinaciclib DRUG

intravenous

Also known as: MK-7965, SCH-727965

Venetoclax + Dinaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol.

You may not qualify if:

• Known central nervous system leukemia
• Severe chronic obstructive pulmonary disease (COPD) with hypoxemia
• History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment.
• Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.
• History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
• Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• History of tumor lysis syndrome (TLS) due to previous exposure to venetoclax.

Sponsors & Collaborators

• AbbVie: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (13)

University of Arkansas /ID# 200016

Little Rock, Arkansas, 72205, United States

Location

David Geffen School of Medicin /ID# 200015

Los Angeles, California, 90095, United States

Location

The University ofChicago /ID# 200017

Chicago, Illinois, 60637, United States

Location

University of Maryland School of Medicine /ID# 204015

Baltimore, Maryland, 21201-1544, United States

Location

Wake Forest Baptist Medical Center /ID# 200288

Winston-Salem, North Carolina, 27157-0001, United States

Location

The Ohio State University /ID# 200668

Columbus, Ohio, 43210, United States

Location

University of Texas MD Anderson Cancer Center /ID# 205215

Houston, Texas, 77030, United States

Location

Gold coast University Hospital /ID# 202759

Southport, Queensland, 4215, Australia

Location

Royal Hobart Hospital /ID# 202763

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre /ID# 202762

Melbourne, Victoria, 3168, Australia

Location

Hospital Universitario Ramon y Cajal /ID# 201729

Madrid, 28034, Spain

Location

Hospital Universitario de Salamanca /ID# 201728

Salamanca, 37711, Spain

Location

Hospital Universitario y Politecnico La Fe /ID# 202318

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Neoplasms; Leukemia, Myeloid, Acute; Recurrence

Interventions

venetoclax; dinaciclib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: March 30, 2018
• Study Start: July 23, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 30, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); ES (3); AU (3)