Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).

NCT03298984 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TPI-ALV-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this Phase I study is to determine the safety and tolerability including the maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Alvocidib

  Determine the safety and tolerability including the maximum tolerated dose (MTD) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

  During the first cycle

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) of Alvocidib

  Determine the safety and tolerability including dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

  During the first cycle

Secondary Outcomes (2)

• Antileukemic Activity of Alvocidib Plus 7+3 - Response to Treatment Based on 2017 ELN Response Criteria

  Best response during duration of study

• Recommended Phase 2 Dose (RP2D) of Alvocidib in Combination With 7+3

  During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days

Other Outcomes (1)

• Minimal Residual Disease (MRD) Using Standardized Techniques

  During duration of study

Study Arms (1)

Alvocidib and Cytarabine/Daunorubicin

EXPERIMENTAL

The starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.

Drug: Alvocidib; Drug: Cytarabine; Drug: Daunorubicin

Interventions

Alvocidib DRUG

IV bolus followed by IV infusion

Alvocidib and Cytarabine/Daunorubicin

Cytarabine DRUG

continuous infusion

Alvocidib and Cytarabine/Daunorubicin

Daunorubicin DRUG

IV bolus

Alvocidib and Cytarabine/Daunorubicin

Eligibility Criteria

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

You may qualify if:

• Be between the ages of ≥18 and ≤65 years
• Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria with ≥20% bone marrow blasts based on histology or flow cytometry
• Be newly diagnosed and previously untreated
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
• Have a serum creatinine level ≤1.8 mg/dL
• Have an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)
• Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)
• Have a left ventricular ejection fraction (LVEF) \>45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• 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 prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of study drug.
• Be able to comply with the requirements of the entire study.
• Provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)

You may not qualify if:

• Received any previous treatment for AML
• Diagnosed with APL-M3 or CBF-AML
• Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.
• Received \>200 mg/m2 equivalents of daunorubicin
• Have a peripheral blast count of \>30,000/mm3 (may use hydroxyurea as in #3 above)
• Have active central nervous system (CNS) leukemia
• Have evidence of uncontrolled disseminated intravascular coagulation
• Have an active, uncontrolled infection
• Have other life-threatening illness
• Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
• Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
• Are pregnant and/or nursing

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (3)

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Zeidner JF, Lee DJ, Frattini M, Fine GD, Costas J, Kolibaba K, Anthony SP, Bearss D, Smith BD. Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia. Clin Cancer Res. 2021 Jan 1;27(1):60-69. doi: 10.1158/1078-0432.CCR-20-2649. Epub 2020 Sep 30.

  PMID: 32998965 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

alvocidib; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Susan Smith
• Organization: Sumitomo Dainippon Pharma Oncology, Inc.

Susan.smith@sdponcology.com

2104147702

Study Officials

• Stephen Anthony, DO

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: September 25, 2017
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: November 15, 2023
• Results First Posted: May 24, 2021

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)