Clinical Trial: NCT03586609 - My Cancer Genome

NCT03586609

Description:

This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that has previously not been treated. Drugs used in chemotherapy, such as venetoclax, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, cladribine, low dose cytarabine induction followed by cladribine, low dose cytarabine, and azacitidine consolidation may work better in treating patients with acute myeloid leukemia.

Related Conditions:

Acute Myeloid Leukemia

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03586609

Trial Eligibility

Document

Title

Brief Title: Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Official Title: Phase II Study of Venetoclax Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Cladribine Plus LDAC Alternating With 5-Azacitidine With Venetoclax in Patients With Untreated AML

Clinical Trial IDs

ORG STUDY ID: 2018-0020
SECONDARY ID: NCI-2018-01318
SECONDARY ID: 2018-0020
NCT ID: NCT03586609

Conditions

Acute Myeloid Leukemia

Interventions

Drug	Synonyms	Arms
Azacitidine	5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza	Treatment (cladribine, cytarabine, venetoclax, azacitidine)
Cladribine	2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251	Treatment (cladribine, cytarabine, venetoclax, azacitidine)
Cytarabine	.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453	Treatment (cladribine, cytarabine, venetoclax, azacitidine)
Venetoclax	ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto	Treatment (cladribine, cytarabine, venetoclax, azacitidine)

Purpose

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess the complete response (CR/complete response with incomplete recovery [CRi]) rate
      of patients with acute myeloid leukemia (AML) treated with venetoclax combined with
      cladribine (2-CDA) plus low-dose cytarabine (LDAC) alternating with 5-azacytidine.

      SECONDARY OBJECTIVES:

      I. To assess overall survival (OS) of patients with AML treated with venetoclax added to
      cladribine plus LDAC alternating with 5-azacytidine.

      II. To assess the disease free survival (DFS) patients with AML treated with venetoclax added
      to cladribine plus LDAC alternating with 5-azacytidine and achieved a complete response
      (CR/CRi).

      III. To assess the overall response rate of patients with AML treated with venetoclax added
      to cladribine plus LDAC alternating with 5-azacytidine.

      IV. To assess toxicity and induction mortality of patients with AML treated with venetoclax
      added to cladribine plus LDAC alternating with 5-azacytidine.

      EXPLORATORY OBJECTIVES:

      I. Evaluate and determine venetoclax pharmacokinetics (pK) in presence or absence of
      concomitantly administered drugs such as posaconazole, voriconazole, isafuconazole, and
      fluconazole.

      II. Investigate the correlation between venetoclax pK with toxicities and efficacy.

      III. Investigate the correlation of baseline cytogenetic and mutational data with likelihood
      of response and resistance to the regimen.

      IV. Evaluate the depth of response with minimal residual disease (MRD) testing and correlate
      with long term outcome.

      OUTLINE:

      INDUCTION: Patients receive cladribine intravenously (IV) daily over 1-2 hours on days 1-5,
      cytarabine subcutaneously (SC) twice daily (BID) on days 1-10, and venetoclax orally (PO)
      daily on days 1-21. Treatment continues for 28 days in the absence of disease progression or
      unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a
      second induction cycle. Patients who do not achieve CR or CRi after second induction cycle
      may proceed to cycle 3 of consolidation per investigator.

      CONSOLIDATION/MAINTENANCE:

      Patients who achieve CR or CRi after cycle 1 of induction receive cladribine IV over 1-2
      hours daily on days 1-3, cytarabine SC BID on days 1-10, and venetoclax PO once daily (QD) on
      days 1-21 of cycle 2. All patients receive cladribine IV daily over 1-2 hours of cycles 5-6,
      9-10, 13-14, and 17-18, cytarabine SC BID on days 1-3 of cycles 5-6, 9-10, 13-14, and 17-18,
      venetoclax PO QD on days 1-21 of cycle 3-18, and azacitidine SC daily or IV over 30-60
      minutes on days 1-7 of cycles 3-4, 7-8, 1-12, and 15-18. Treatment repeats every 28 days for
      up to 18 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6-12 months for 5 years.

Trial Arms

Name	Type	Description	Interventions
Treatment (cladribine, cytarabine, venetoclax, azacitidine)	Experimental	See Detailed Description.	Azacitidine Cladribine Cytarabine Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with previously untreated acute myeloid leukemia (AML). Prior therapy with
             hydroxyurea, hematopoietic growth factors, HMA, all-trans retinoic acid (ATRA), or a
             total dose of cytarabine up to 2 g (for emergency use for stabilization) is allowed.

          -  Patients aged < 50 years who are unsuitable for standard induction therapy may be
             eligible after discussion with primary investigator.

          -  Bilirubin =< 2 mg/dL. Unless liver enzyme abnormalities are determined by the treating
             Doctor of Medicine (MD) and principal investigator (PI) to be due to leukemic
             infiltration.

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (AL)T =< 3 x ULN.
             Unless liver enzyme abnormalities are determined by the treating MD and PI to be due
             to leukemic infiltration.

          -  Creatinine =< 1.5 x upper limit of normal (ULN).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.

          -  A negative urine pregnancy test is required within 1 week for all women of
             childbearing potential prior to enrolling on this trial.

          -  Patient must have the ability to understand the requirements of the study and signed
             informed consent. A signed informed consent by the patient or his legally authorized
             representative is required prior to their enrollment on the protocol.

        Exclusion Criteria:

          -  Pregnant women are excluded from this study because the agents used in this study have
             the potential for teratogenic or abortifacient effects. Because there is a potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             the chemotherapy agents, breastfeeding should also be avoided.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             uncontrolled infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Patient with documented hypersensitivity to any of the components of the chemotherapy
             program.

          -  Men and women of childbearing potential who do not practice contraception. Women of
             childbearing potential and men must agree to use contraception prior to study entry
             and for the duration of study participation.

          -  Prior therapy with venetoclax.

          -  Patients with a diagnosis of acute promyelocytic leukemia (AML-M3) will be excluded
             from this study.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	50 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Rate of complete response (CR/complete response with incomplete recovery [CRi])
Time Frame:	Up to completion of cycle 2 (each cycle is 28 days)
Safety Issue:
Description:	The optimum two-stage design will be implemented. Will be estimated along with the 95% confidence intervals.

Secondary Outcome Measures

Measure:	Overall response rate
Time Frame:	Up to 5 years
Safety Issue:
Description:	Will be estimated along with the 95% confidence intervals.

Measure:	Overall survival (OS)
Time Frame:	Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years
Safety Issue:
Description:	Kaplan-Meier method will be used to assess the OS probabilities. The median OS will be reported, along with the 95% confidence intervals.

Measure:	Disease-free survival (DFS)
Time Frame:	Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years
Safety Issue:
Description:	Kaplan-Meier method will be used to assess the DFS probabilities. The median DFS will be reported, along with the 95% confidence intervals.

Measure:	Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:	Up to 5 years
Safety Issue:
Description:	The Bayesian approach will be implemented for toxicity monitoring, where toxicity is defined as any grade 3 or higher non-hematological toxicity which is at least possibly related to the treatment that occurs during the first 2 cycles of treatment. Safety data will be summarized by category, severity and frequency.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

May 25, 2021

Clinical Trials /

Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia