search
Back to results

Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant

Primary Purpose

Recurrent Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Venetoclax
Decitabine
Cedazuridine
Bone Marrow Aspiration and Biopsy
Biospecimen Collection
Sponsored by
Sanjay Mohan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements History of morphologically confirmed AML (per World Health Organization [WHO] diagnostic criteria) with evidence of disease recurrence (>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia [MDS/CMML]) who relapse with AML are eligible to enroll White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed) A bone marrow biopsy must be performed and tissue collected for entrance to the trial Eastern Cooperative Oncology Group Performance Status of 0 - 2 Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN) Total bilirubin < 1.5 x ULN * Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of < 3 x ULN Calculated creatinine clearance >= 30 ml/min (per the Cockroft-Gault formula) Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications Exclusion Criteria: Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor Anticancer therapy, including investigational agents =< 2 weeks or =< 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted) Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]5.0), excluding alopecia or fatigue History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible Radiation therapy or major surgery within 3 weeks of signing consent Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption Active documented central nervous system leukemia Concurrent treatment with a non-permitted concomitant medication Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ Pregnancy or breastfeeding females Known chronic alcohol or drug abuse Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents

Sites / Locations

  • Vanderbilt University/Ingram Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (Venetoclax, DEC-C)

Arm Description

Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Outcomes

Primary Outcome Measures

Composite complete response (CR) rate (CR/complete response with partial recovery of peripheral blood counts [CRh]/complete remission with incomplete hematological recovery [CRi])
Categorical variables (e.g., objective response) will be summarized in frequency tables and compared among patient subgroups using the chi-square test. Linear regression and logistic (or ordinal logistic) regression will be used to construct multivariable models for continuous, binary, and ordinal variables, as appropriate. In addition to ORR, the distributions of progression-free and overall survival will be estimated using the Kaplan-Meier method. We will consider statistical comparisons statistically, but not necessarily clinically, significant for p<0.05.

Secondary Outcome Measures

Rate of partial response (PR) following treatment with DEC-C/venetoclax
Rate of morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax
Rate of relapse free survival
Rate of overall survival
The distributions of progression-free and overall survival will be estimated using the Kaplan-Meier method.
Incidence of adverse events
Rate of measurable residual disease negativity in patients achieving a CR

Full Information

First Posted
March 22, 2023
Last Updated
September 17, 2023
Sponsor
Sanjay Mohan
Collaborators
National Comprehensive Cancer Network, Taiho Oncology, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05799079
Brief Title
Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant
Official Title
Phase 2 Study of Decitabine and Cedazuridine in Combination With Venetoclax for AML Relapse After Allogeneic Hematopoietic Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
November 2027 (Anticipated)
Study Completion Date
November 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sanjay Mohan
Collaborators
National Comprehensive Cancer Network, Taiho Oncology, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial tests how well decitabine and cedazuridine (DEC-C) works in combination with venetoclax in treating acute myeloid leukemia (AML) in patients whose AML has come back after a period of improvement (relapse) after a donor stem cell transplant. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving DEC-C in combination with venetoclax may kill more cancer cells in patients with relapsed AML.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the effect of DEC-C/venetoclax on the investigator-assessed composite complete remission (CR) rate (CR/complete remission with partial hematologic recovery [CRh]/complete remission with incomplete hematologic recovery [CRi]). SECONDARY OBJECTIVES: I. To assess the rate of partial response (PR) and morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax. II. To assess the relapse free survival of patients treated with DEC-C/venetoclax. III. To assess overall survival of patients treated with DEC-C/venetoclax. IV. To assess the safety and tolerability of DEC-C/venetoclax in the post-hematopoietic cell transplant (HCT) setting. V. To assess the rates of measurable residual disease negativity in patients achieving a CR. OUTLINE: Patients receive venetoclax orally (PO) daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (Venetoclax, DEC-C)
Arm Type
Experimental
Arm Description
Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
Given by mouth
Intervention Type
Drug
Intervention Name(s)
Decitabine
Intervention Description
Given by mouth
Intervention Type
Drug
Intervention Name(s)
Cedazuridine
Intervention Description
Given by mouth
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Aspiration and Biopsy
Intervention Description
Undergo bone marrow biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Intervention Description
Undergo blood sample collection
Primary Outcome Measure Information:
Title
Composite complete response (CR) rate (CR/complete response with partial recovery of peripheral blood counts [CRh]/complete remission with incomplete hematological recovery [CRi])
Description
Categorical variables (e.g., objective response) will be summarized in frequency tables and compared among patient subgroups using the chi-square test. Linear regression and logistic (or ordinal logistic) regression will be used to construct multivariable models for continuous, binary, and ordinal variables, as appropriate. In addition to ORR, the distributions of progression-free and overall survival will be estimated using the Kaplan-Meier method. We will consider statistical comparisons statistically, but not necessarily clinically, significant for p<0.05.
Time Frame
Up to 24 months post-treatment.
Secondary Outcome Measure Information:
Title
Rate of partial response (PR) following treatment with DEC-C/venetoclax
Time Frame
Up to 24 months post-treatment.
Title
Rate of morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax
Time Frame
Up to 24 months post-treatment.
Title
Rate of relapse free survival
Time Frame
Up to 24 months post-treatment.
Title
Rate of overall survival
Description
The distributions of progression-free and overall survival will be estimated using the Kaplan-Meier method.
Time Frame
Up to 24 months post-treatment.
Title
Incidence of adverse events
Time Frame
Up to 24 months post-treatment.
Title
Rate of measurable residual disease negativity in patients achieving a CR
Time Frame
Up to 24 months post-treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements History of morphologically confirmed AML (per World Health Organization [WHO] diagnostic criteria) with evidence of disease recurrence (>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia [MDS/CMML]) who relapse with AML are eligible to enroll White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed) A bone marrow biopsy must be performed and tissue collected for entrance to the trial Eastern Cooperative Oncology Group Performance Status of 0 - 2 Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN) Total bilirubin < 1.5 x ULN * Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of < 3 x ULN Calculated creatinine clearance >= 30 ml/min (per the Cockroft-Gault formula) Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications Exclusion Criteria: Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor Anticancer therapy, including investigational agents =< 2 weeks or =< 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted) Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]5.0), excluding alopecia or fatigue History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible Radiation therapy or major surgery within 3 weeks of signing consent Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption Active documented central nervous system leukemia Concurrent treatment with a non-permitted concomitant medication Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ Pregnancy or breastfeeding females Known chronic alcohol or drug abuse Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vanderbilt-Ingram Services for Timely Access
Phone
800-811-8480
Email
cip@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanjay Mohan, MD
Organizational Affiliation
Vanderbilt University/Ingram Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanderbilt-Ingram Service for Timely Access
Phone
800-811-8480
Email
cip@vumc.org
First Name & Middle Initial & Last Name & Degree
Sanjay Mohan, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant

We'll reach out to this number within 24 hrs