Not provided
Not provided
Not provided
Not provided
Not provided
Study terminated 7/23/2019 due to limited participation and testing challenges.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) following induction chemotherapy. However, a large majority subsequently relapse and succumb to the disease. Currently, cytogenetics and molecular aberrations are the best prognostic indicators; however, these factors cannot prognosticate accurately for individual patients. Overall, the majority of patients with favorable or intermediate-risk AML will experience relapse. Prognosis after relapse is dismal with a five-year overall survival rate of less than 10%. A leukemia stem cell (LSC) paradigm may explain this failure of CR to reliably translate into cure. This study is undertaken to determine whether the presence of LSCs has prognostic value as well as to determine whether the presence of LSCs has predictive value. This study has an observational component, whereby we intent evaluate whether the presence or absence of LSCs is prognostic. This study also has an interventional component in which it uses LSC status to determine whether favorable and intermediate risk AML patients in CR receive consolidation with chemotherapy or allogeneic HCT.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evaluable Cohort - Transplant Arm | Other | Other - Standard of Care Consolidation (HCT) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
|
|
| Evaluable Cohort - Consolidation Chemo Arm | Other | Other - Standard of Care Consolidation (cytarabine-based chemo) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
|
|
| Observational Cohort 1 | No Intervention | Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic HCT | Procedure | Allogeneic HCT |
|
| Measure | Description | Time Frame |
|---|---|---|
| 2 Year Relapse Free Survival (RFS) | Comparison of 2 year RFS in patient with detectable LSCs in the marrow at the end of consolidation to the 2 year RFS of patients without detectable LSCs. IWG Criteria (Cheson 2003) was utilized to classify relapse, with relapse defined as ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease, or disease presence determined by a physician upon clinical assessment. | 2 years |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Michael Grunwald, M.D. | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Evaluable Cohort - Transplant Arm | Standard of Care Consolidation (HCT) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Allogeneic HCT |
| FG001 | Evaluable Cohort - Consolidation Chemo Arm | Standard of Care Consolidation (cytarabine-based chemo) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy |
| FG002 | Observational Cohort 1 | Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1. |
| FG003 | Observational Cohort 2 | Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria:
Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy. HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Evaluable Cohort - Transplant Arm | Standard of Care Consolidation (HCT) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age at date of consent |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 2 Year Relapse Free Survival (RFS) | Comparison of 2 year RFS in patient with detectable LSCs in the marrow at the end of consolidation to the 2 year RFS of patients without detectable LSCs. IWG Criteria (Cheson 2003) was utilized to classify relapse, with relapse defined as ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease, or disease presence determined by a physician upon clinical assessment. | The primary efficacy analyses will be conducted on the subset of subjects who were included in the evaluable cohort (HCT or chemo treatment arm) and who also had a successful/interpretable end of consolidation eLSC assay. This excludes subjects in OC1 and 2, as they did not achieve CR to induction or did not have the immunophenotype of interest. | Posted | Count of Participants | Participants | 2 years |
|
Graft Versus Host Disease (GVHD) events were collected from the time of consolidation HCT through long term follow-up (up to approximately 5 years). - Acute GVHD: Confirmed GVHD within 100 days of HCT. - Chronic GVHD: Confirmed GVHD 100 days or more after HCT.
Both cytarabine-based consolidation chemo and HCT are considered standard of care for this disease population. With the exception of GVHD, an event of clinical interest, adverse events experienced by the subjects were not recorded in the dataset or included in the safety analysis. Each occurrence of GVHD, in evaluable subjects who received HCT, was graded by the investigator according to accepted institutional practice: CIBMTR grading for Acute GVHD; NIH Consensus criteria for Chronic GVHD.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Evaluable Cohort - Transplant Arm | Standard of Care Consolidation (HCT) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Allogeneic HCT: Allogeneic HCT |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Symanowski; Chair, Department of Cancer Biostatistics | Levine Cancer Institute | 9804422371 | james.symanowski@atriumhealth.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 27, 2017 | Aug 13, 2019 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D014180 | Transplantation |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D060830 | Consolidation Chemotherapy |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Observational Cohort 2 | No Intervention | Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria:
Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy. HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT. |
| Consolidation chemotherapy | Drug | Cytarabine-based consolidation chemotherapy |
|
|
| Early Study Termination |
|
| BG001 | Evaluable Cohort - Consolidation Chemo Arm | Standard of Care Consolidation (cytarabine-based chemo) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy |
| BG002 | Observational Cohort 1 | Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1. |
| BG003 | Observational Cohort 2 | Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria:
Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy. HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Age at date of consent | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| AML Risk Level (prior to induction) | AML risk level is determined from bone marrow biopsy performed at AML diagnosis
| Count of Participants | Participants |
|
| Immunophenotype at LSC0 | LSC0: Diagnostic bone marrow sample or peripheral blood sample that the leukemia stem cell assay is performed on. LSC0 occurs prior to induction therapy for diagnostic purposes and identifies the subject's immunophenotype at diagnosis. | Count of Participants | Participants |
|
| LSC0 Status (prior to induction) | LSC0: Diagnostic bone marrow sample or peripheral blood sample that the leukemia stem cell assay is performed on. LSC0 occurs prior to induction therapy for diagnostic purposes. | Count of Participants | Participants |
|
| Deletion 5 or 5q | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| Deletion 7 or 7q | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| KNMT2A | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| inv(3) or t(3;3) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| t(6;9) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| t(9;22) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| t(8;21) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| inv(16 or t(16;16) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| Plus 8 | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| Plus 21 | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| t(9;11) | Cytogenetic and/or molecular abnormalities determined at diagnosis (LSC0 time point) | Count of Participants | Participants |
|
| LSC1 Status (post induction, at enrollment) | LSC1: Bone marrow sample that the post-induction leukemia stem cell (LSC) assay is performed on. LSC1 occurs following induction therapy and at the time of complete remission assessment (End of Induction visit). | Count of Participants | Participants |
|
| OG001 | eLSC- (Evaluable Cohort) | Of the subjects enrolled in the evaluable cohort (either allo HCT or consolidation chemotherapy), those who had leukemia stem cells not detected post-consolidation. Note, eLSC indicates the time point after consolidation. |
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | Evaluable Cohort - Consolidation Chemo Arm | Standard of Care Consolidation (cytarabine-based chemo) Enrolled subjects that will contribute to the population of subjects who are evaluable for the primary and secondary objectives. This will not include any subjects who end up in either observational cohort. To be included in the evaluable cohort, the subject must meet the following requirements:
Consolidation chemotherapy: Cytarabine-based consolidation chemotherapy | 1 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Observational Cohort 1 | Enrolled subjects who do not achieve a CR to induction therapy, regardless of diagnostic phenotype. Following completion of induction therapy and remission bone marrow aspirate, if a subject is determined to not have achieved a complete remission to induction therapy, he or she would be included in observational cohort 1. | 0 | 4 | 0 | 4 | 0 | 4 |
| EG003 | Observational Cohort 2 | Enrolled subjects who achieve a CR to induction therapy but meet one or more of the following criteria:
Final investigator determination of fit-ness can occur at any time until the start of consolidation therapy. HMA-based induction subjects will not receive consolidation cytarabine-based chemotherapy as part of the evaluable cohort if they do not receive HCT. | 4 | 7 | 0 | 7 | 0 | 7 |
Not provided
Not provided
Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |