Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).
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|ClinicalTrials.gov Identifier: NCT03298984|
Recruitment Status : Completed
First Posted : October 2, 2017
Results First Posted : May 24, 2021
Last Update Posted : May 24, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Alvocidib Drug: Cytarabine Drug: Daunorubicin||Phase 1|
• 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
- 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
• 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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||September 25, 2017|
|Actual Primary Completion Date :||March 20, 2020|
|Actual Study Completion Date :||March 20, 2020|
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
- 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
- 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
- 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.
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298984
|United States, Maryland|
|Sidney Kimmel Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21287|
|United States, New York|
|New York, New York, United States, 10032|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|Study Director:||Stephen Anthony, DO||Sumitomo Dainippon Pharma Oncology, Inc|