Alvocidib Biomarker-driven Phase 2 AML Study

NCT ID: NCT02520011

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-14
• Study Completion Date: 2020-02-12

Brief Summary

The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) of ACM (Alvocidib/Cytarabine/Mitoxantrone) compared to CM (Cytarabine/Mitoxantrone) treatment in refractory or relapsed AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow.

Detailed Description

In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will receive treatment with ACM.

In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ACM (Stage 1 / Stage 2)

A: alvocidib, 30 mg/m2 as a 30 minute intravenous (IV) bolus followed by 60 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3; C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 6-8; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

Group Type: EXPERIMENTAL

Alvocidib

Intervention Type: DRUG

Cytarabine

Intervention Type: DRUG

Mitoxantrone

Intervention Type: DRUG

CM (Stage 2)

C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 1-3; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

Group Type: ACTIVE_COMPARATOR

Cytarabine

Intervention Type: DRUG

Mitoxantrone

Intervention Type: DRUG

Interventions

Alvocidib

Intervention Type: DRUG

Cytarabine

Intervention Type: DRUG

Mitoxantrone

Intervention Type: DRUG

Other Intervention Names

ara-c; mitoxantrone hydrochloride

Eligibility Criteria

Inclusion Criteria

1. Be between the ages of ≥18 and ≤65 years

2. Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry

3. Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR or CRi after treatment with an intensive regimen (eg, anthracycline/cytarabine ± etoposide, gemtuzumab ozogamicin, or cladribine).

*Induction therapy may involve 1 or 2 cycles of the same regimen. Efficacy assessment of induction therapy must be >21 days from the start of the previous induction cycle.

4. Demonstrate MCL-1 dependence of ≥30% by mitochondrial profiling in bone marrow.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

6. Have a serum creatinine level ≤1.8 mg/dL

7. Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)

8. Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)

9. Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

10. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate during and for at least 6 months after completion of study therapy.

11. Be able to comply with the requirements of the entire study.

12. Provide written informed consent prior to any study related procedure.

Exclusion Criteria

1. Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see #5 below).

2. Received any previous treatment with alvocidib or any other CDK inhibitor

3. Received a hematopoietic stem cell transplant within the previous 2 months

4. Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days

5. Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.

6. Received >360 mg/m2 equivalents of daunorubicin

7. Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)

8. Received antileukemic therapy within the last 3 weeks (with the exception of hydroxyurea or if the patient has definite refractory disease). Refractory patients who received therapy within the last 3 weeks may be eligible with prior approval of the Medical Monitor.

9. Diagnosed with acute promyelocytic leukemia (APL, M3)

10. Have active central nervous system (CNS) leukemia

11. Have evidence of uncontrolled disseminated intravascular coagulation

12. Have an active, uncontrolled infection

13. Have other life-threatening illness

14. Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia

15. Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.

16. Are pregnant and/or nursing

17. Have received any live vaccine within 14 days prior to first study drug administration.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Anthony, DO

Role: STUDY_DIRECTOR

Sumitomo Pharma America, Inc.

Locations

Honor Health Research Institute

Scottsdale, Arizona, United States

University of California Los Angeles (UCLA)

Los Angeles, California, United States

University of California San Diego UCSD

San Diego, California, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Medical Center

Westwood, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Morristown Cancer Center

Morristown, New Jersey, United States

Roswell Park Cancer Center Institute

Buffalo, New York, United States

Hudson Valley Cancer Center

Hawthorne, New York, United States

Columbia University Medical Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke

Durham, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

West Penn Allegheny Hospital

Pittsburgh, Pennsylvania, United States

Baylor Sammons Cancer Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Hospital Regional Universitario de Malaga

Málaga, Malaga, Spain

Complejo Hospitalario Universitario de Albacete

Albacete, , Spain

Institut Catala d'Oncologia

Badalona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital Universitario Central de Asturias - HUCA

Oviedo, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

University Hospitals of Wales

Cardiff, Wales, United Kingdom

Univ Hospital of Bristol

Bristol, , United Kingdom

Guys Hospital St. Thomas

London, , United Kingdom

Countries

United States; Canada; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TPI-ALV-201

Identifier Type: -

Identifier Source: org_study_id