Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Alvocidib

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

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.

Stephen Anthony, DO

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

Primary Objective:

• To determine the safety and tolerability including the maximum tolerated 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

Secondary Objectives:

* To observe patients for any evidence of antileukemic activity of alvocidib plus 7+3 using the 2017 ELN response criteria
* To establish the Recommended Phase 2 Dose (RP2D) for future studies with alvocidib in combination with 7+3

Exploratory Objective:

• To assess levels of minimal residual disease (MRD) using standardized techniques (ie, multiparametric flow cytometry \[MPFC\] and next generation sequencing \[NGS\] and evaluate other potential biomarkers including, but not limited to, MCL-1 dependency.

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

A Phase 1, Open-label, Dose-escalation, Safety and Biomarker Prediction of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Percentage of participants with a CRMRD- response at the end of Cycle 1

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

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

CR: Measurable residual disease is positive or unknown; BM blasts (bls) \<5%; no circulating bls and bls w/ Auer rods; no extramedullary disease; ANC \>1.0 x 109/L; platelets \>100 x 109/L. CRMRD-: CR w/ negativity genetic marker. CRi: CR except residual neutropenia or thrombocytopenia. MLFS: BM bls \<5%; no bls with Auer rods; no extramedullary disease; no hematologic recovery required. PR: all hematologic CR criteria; decrease (dec) BM bls % to 5-25%; dec pretreatment BM bls % by \>50%. SD: no CRMRD-/CR/CRi/PR/MLFS; PD criteria not met. PD: increase (inc) BM bls % and/or inc absolute bls in blood: 50% inc BM bls over baseline (\>15% point inc required in cases w/ \<30% bls at baseline or persistent BM bls % of \>70% over at least 3 months; without at least 100% improvement in ANC to absolute level \[\>0.5 x 109/L and/or platelet count to \>50 x 109/L non-transfused); or \>50% inc in peripheral bls to \>25 x 109/L (in the absence of differentiation syndrome); or new extramedullary disease.

The dose at which \< 1 of 6 patients experience a DLT during Cycle 1 with the next higher dose having at least 2 of 3 to 6 patients experiencing a DLT during Cycle 1

Sumitomo Pharma America, Inc.

Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

Alvocidib 20mg/m2 bolus followed by 30 mg/m2 IV infusion over 4 hours

Alvocidib 20/30 mg/m2 (N=3)

Alvocidib 30 mg/m2 bolus followed by 40 mg/m2 IV infusion over 4 hours

Alvocidib 30/40 mg/m2 (N=3)

Alvocidib 30 mg/m2 bolus followed by 50 mg/m2 IV infusion over 4 hours

Alvocidib 30/50 mg/m2 (N=3)

Alvocidib 30 mg/m2 bolus followed by 60 mg/m2 IV infusion over 4 hours

Alvocidib 30/60 mg/m2 (N=23)

Alvocidib 20 mg/m2 bolus followed by 30 mg/m2 IV infusion over 4 hours

Alvocidib 20/30 mg/m2

Alvocidib 30/40 mg/m2

Alvocidib 30/50 mg/m2

Alvocidib 30/60 mg/m2

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Susan Smith

Bolus

IV infusion

All participants who received at least 1 dose of Alvocidib, either at 20 mg/m2 bolus followed by 30 mg/m2 IV infusion over 4 hours, 30 mg/m2 bolus followed by 40 mg/m2 IV infusion over 4 hours, 30 mg/m2 bolus followed by 50 mg/m2 IV infusion over 4 hours, or 30 mg/m2 bolus followed by 60 mg/m2 IV infusion over 4 hours

All Participants

Maximum Tolerated Dose (MTD) of Alvocidib

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

Complete Remission MRD Negative (CRMRD-)

Complete Remission MRD Positive or Unknown (CR)

Partial Remission (PR)

Stable Disease

Progressive Disease (PD)

Not Evaluated

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

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

Minimal Residual Disease (MRD) Using Standardized Techniques

Overall Study

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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