- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03298984
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Sidney Kimmel Cancer Center at Johns Hopkins
-
-
New York
-
New York, New York, United States, 10032
- Columbia University
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27599
- University of North Carolina
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
To be eligible for participation in the study, patients must meet all of the following inclusion criteria:
- 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.)
Exclusion Criteria:
Patients meeting any one of these exclusion criteria will be prohibited from participating in this study.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Alvocidib and Cytarabine/Daunorubicin
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.
|
IV bolus followed by IV infusion
continuous infusion
IV bolus
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Alvocidib
Time Frame: During the first cycle
|
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
Time Frame: During the first cycle
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antileukemic Activity of Alvocidib Plus 7+3 - Response to Treatment Based on 2017 ELN Response Criteria
Time Frame: Best response during duration of study
|
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.
|
Best response during duration of study
|
Recommended Phase 2 Dose (RP2D) of Alvocidib in Combination With 7+3
Time Frame: During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days
|
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
|
During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimal Residual Disease (MRD) Using Standardized Techniques
Time Frame: During duration of study
|
Percentage of participants with a CRMRD- response at the end of Cycle 1
|
During duration of study
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Stephen Anthony, DO, Sumitomo Pharma America, Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Cytarabine
- Daunorubicin
- Alvocidib
Other Study ID Numbers
- TPI-ALV-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Massachusetts General HospitalExelixisCompletedRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Massachusetts General HospitalCelgene CorporationTerminatedAcute Myelogenous Leukemia | Acute Myeloid Leukemia (AML) | Acute Myelocytic Leukemia | Acute Granulocytic Leukemia | Acute Non-Lymphocytic LeukemiaUnited States
Clinical Trials on Alvocidib
-
National Cancer Institute (NCI)CompletedLymphoma | Small Intestine Cancer | Prostate Cancer | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedEndometrial CancerUnited States, Canada, Norway, United Kingdom, Australia
-
National Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)CompletedLymphomaUnited States
-
Sumitomo Pharma America, Inc.TerminatedAcute Myeloid Leukemia (AML)United States
-
NCIC Clinical Trials GroupCompleted
-
Southwest Oncology GroupNational Cancer Institute (NCI)CompletedKidney CancerUnited States
-
National Cancer Institute (NCI)Completed
-
NCIC Clinical Trials GroupCompletedSarcomaCanada, United States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)CompletedLeukemiaUnited States