Alvocidib Biomarker-driven Phase 2 AML Study
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| ClinicalTrials.gov Identifier: NCT02520011 |
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Recruitment Status :
Terminated
(Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete.)
First Posted : August 11, 2015
Results First Posted : July 15, 2021
Last Update Posted : April 6, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia | Drug: Alvocidib Drug: Cytarabine Drug: Mitoxantrone | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 104 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2, Randomized, Biomarker-driven Clinical Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With MCL-1 Dependence ≥30% |
| Actual Study Start Date : | March 14, 2016 |
| Actual Primary Completion Date : | February 12, 2020 |
| Actual Study Completion Date : | February 12, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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
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Drug: Alvocidib Drug: Cytarabine Other Name: ara-c Drug: Mitoxantrone Other Name: mitoxantrone hydrochloride |
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Active Comparator: 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
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Drug: Cytarabine
Other Name: ara-c Drug: Mitoxantrone Other Name: mitoxantrone hydrochloride |
- Complete Response (CR) Rate in Patients With Relapsed or Refractory AML [ Time Frame: Best response after at least 1 cycle through study completion approximately 4 years ]
Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group (IWG) Criteria and 2010 European LeukemiaNet (EN) criteria in patients with relapsed or refractory AML with MCL-1 dependence >30% and in Stage 2 by the 2017 ELN criteria.
The study was terminated in January 2020 due to a steady and marked reduction in enrollment. Thus, the efficacy endpoints could not be analyzed. As sufficient efficacy results were not available to analyze patients based on the percentage of MCL-1 dependency the treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received the ACM vs CM regimen and their disease stages at study entry.
- Response to Treatment [ Time Frame: Best response after at least 1 cycle through study completion approximately 4 years ]To determine if treatment with ACM can induce CR in patients with relapsed or refractory AML with MCL-1 dependence of >30% who failed to achieve CR following 1 cycle of CM
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry
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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.
- Demonstrate MCL-1 dependence of ≥30% by mitochondrial profiling in bone marrow.
- 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)/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 during and for at least 6 months after completion of study therapy.
- Be able to comply with the requirements of the entire study.
- Provide written informed consent prior to any study related procedure.
Exclusion Criteria:
- 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).
- Received any previous treatment with alvocidib or any other CDK inhibitor
- Received a hematopoietic stem cell transplant within the previous 2 months
- Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days
- 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.
- Received >360 mg/m2 equivalents of daunorubicin
- Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)
- 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.
- Diagnosed with acute promyelocytic leukemia (APL, M3)
- 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
- Have received any live vaccine within 14 days prior to first study drug administration.
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): NCT02520011
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| Study Director: | Stephen Anthony, DO | Sumitomo Pharma Oncology, Inc. |
Documents provided by Sumitomo Pharma Oncology, Inc.:
| Responsible Party: | Sumitomo Pharma Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT02520011 |
| Other Study ID Numbers: |
TPI-ALV-201 |
| First Posted: | August 11, 2015 Key Record Dates |
| Results First Posted: | July 15, 2021 |
| Last Update Posted: | April 6, 2022 |
| Last Verified: | April 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Refractory AML Relapsed AML AML |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms Cytarabine Mitoxantrone Alvocidib Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents |
Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Growth Inhibitors Growth Substances Protein Kinase Inhibitors |