Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML

NCT04493099 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2019-1053NCI-2020-05266
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial investigates the side effects and best dose of alvocidib when given together with decitabine and venetoclax and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed), has not responded to previous treatment (refractory), or as frontline treatment for patients unable to receive other therapies (unfit). Alvocidib, decitabine, and venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Overall incidence and severity of all adverse events (Phase I)

  Measured using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 6 years

• Overall response rate (ORR) (Phase II)

  Will estimate the response rate for the combination treatment, along with the 95% credible interval.

  Up to 6 years

Secondary Outcomes (3)

• Duration of response

  Up to 6 years

• Event free survival

  Up to 6 years

• Overall survival

  From treatment start till death or last follow-up, assessed up to 6 years

Study Arms (1)

Treatment (decitabine, alvocidib hydrochloride, venetoclax)

EXPERIMENTAL

INDUCTION: Patients receive decitabine IV over 1 hour on days 1-10, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10, or 1-14, and venetoclax PO QD on days 1-14 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive decitabine IV over 1 hour on days 1-5, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10 or 1-14, and venetoclax PO QD on days 1-10. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Alvocidib Hydrochloride; Drug: Decitabine; Drug: Venetoclax

Interventions

Alvocidib Hydrochloride DRUG

Given IV

Also known as: 4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis-, Flavopiridol Hydrochloride, HL-275, HMR 1275, L-86-8275, L-868275, MDL 107,826A, MDL-107826A

Treatment (decitabine, alvocidib hydrochloride, venetoclax)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, alvocidib hydrochloride, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (decitabine, alvocidib hydrochloride, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of relapsed or refractory acute myeloid leukemia by World Health Organization (WHO) criteria. Unfit/frail patients with newly diagnosed AML are also eligible if not considered good candidates to receive a higher intensity therapy
• A patient is considered unfit or frail if has three or more of the five factor below:
• Unintentional weight loss of 10 pounds or more in a year
• General feeling of exhaustion
• Weakness as measured by grip strength
• Slow walking speed
• Low levels of physical activity
• Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 3
• Total serum bilirubin =\< 2 x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to =\< 3 x ULN
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =\< 3 x ULN; or =\< 5 x ULN in case of suspected leukemic liver involvement
• Serum creatinine =\< 2.0 mg/dl
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (B-HCG) pregnancy test result within 1 week (+/-3 days) prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug. Effective methods of birth control include:
• Birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin)
• Intrauterine devices (IUDs)
• Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide

You may not qualify if:

• Patients with t(15;17) karyotype abnormality or acute promyelocytic leukemia
• History of another primary invasive malignancy that has not been definitively treated and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
• Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Evidence of active cerebral/meningeal disease. Patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment)
• Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV. Patients with a cardiac ejection fraction (as measured by either multigated acquisition scan \[MUGA\] or echocardiogram) \< 45% are excluded
• Patients with uncontrolled, active infections (viral, bacterial, or fungal)
• Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
• Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse
• Allogeneic hematopoietic cell transplantation (HSCT) within 6 months before the start of protocol-specified therapy, or with active acute/chronic graft-versus-host disease (GvHD) requiring systemic treatment; or receiving immunosuppression for GvHD prophylaxis within 2 weeks from the start of study therapy
• Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exception:
• To reduce tumor burden, leukocytosis (circulating blast count) or palliation: Intravenous cytarabine and/or hydroxyurea. No washout is necessary for these agents. Patients must have recovered from acute non hematologic toxicity (to =\< grade 1) of all previous therapy prior to enrollment
• Females who are pregnant or lactating
• Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards
• Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
• Prior treatment with alvocidib

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• http://www.mdanderson.org

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

cytokine inducible SH2-containing protein; alvocidib; Decitabine; Injections; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yesid Alvarado-Valero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 30, 2020
• Study Start: October 1, 2020
• Primary Completion: October 12, 2020
• Study Completion: October 12, 2020
• Last Updated: November 12, 2020

Record last verified: 2020-11

Locations

US (1)