Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Chronic Myelomonocytic Leukemia-2, High Grade Malignant Neoplasm, Myelodysplastic Syndrome, Myelodysplastic Syndrome With Excess Blasts-2, Myeloid Neoplasm, Previously Treated Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
Conditions
Brief summary
This clinical trial studies how well early stem cell transplantation works in treating patients with high-grade myeloid neoplasms that has come back after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as filgrastim, cladribine, cytarabine and mitoxantrone hydrochloride, 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. Giving chemotherapy before a donor peripheral blood cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Early stem cell transplantation may result in more successful treatment for patients with high-grade myeloid neoplasms.
Detailed description
OUTLINE: RE-INDUCTION CHEMOTHERAPY: Patients receive filgrastim subcutaneously (SC) on days 0-5, mitoxantrone hydrochloride intravenously (IV) over 60 minutes on days 1-3, cladribine IV over 2 hours on days 1-5, and cytarabine IV over 2 hours on days 1-5. CONDITIONING REGIMEN: Beginning 14-60 days after re-induction chemotherapy, patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, melphalan IV on days -3 to -2, cyclosporine orally (PO) twice daily (BID) starting on day -3. Sirolimus PO BID starting on day -3 will be given to patients who have matched unrelated donors or mismatched unrelated donors. Patients \>55 years or with significant co-morbidities will only receive melphalan IV on day -2 and will also receive total body irradiation (TBI) on day -1 or day 0. EARLY TRANSPLANT: Patients undergo allogeneic HCT after conditioning regimen on day 0. GVHD PROPHYLAXIS: Patients with matched donors will receive mycophenolate mofetil PO three times daily (TID) on days 0-30, then twice a day (BID) until day 40; and cyclosporine PO BID on days -3 to 96, with a taper until day 150. Patients with matched unrelated donors also receive sirolimus PO BID on days -3 to 150, with a taper until day 180. Patients with mismatched unrelated donors will receive mycophenolate mofetil PO TID on days 0-30, then BID until day 100, with a taper until day 150; cyclosporine PO BID on days -3 to 150, then taper until day 180; and sirolimus BID PO days -3 to 180, then a taper until day 365. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGCyclosporine
Given PO
DRUGCytarabine
Given IV
BIOLOGICALFilgrastim
Given SC
DRUGFludarabine Phosphate
PROCEDUREAllogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic stem cell transplantation
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGCladribine
Given IV
DRUGMelphalan
Given IV
DRUGMitoxantrone Hydrochloride
Given IV
DRUGMycophenolate Mofetil
Given PO
OTHERQuestionnaire Administration
Ancillary studies
DRUGSirolimus
Given PO
RADIATIONTotal-Body Irradiation
Undergo TBI
Given IV
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
INCLUSION CRITERIA (ENROLLMENT) * Relapsed or refractory high-grade myeloid neoplasms, defined as having a blast count of \>= 10% blasts at initial diagnosis; examples include excess blasts (EB)-2, with \>= 10% blasts at initial diagnosis, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML-2); standard definitions of relapse will apply (i.e., characterized by \>= 5% abnormal blasts or blast equivalents as assessed by multiparameter flow cytometry or morphologic examination; peripheral blood blasts or blast equivalents; or extramedullary granulocytic sarcoma, per European LeukemiaNet \[ELN\] 2017 guidelines); bone marrow aspirate/biopsy will be accepted if performed outside University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC); determination of disease status should occur within 30 days of signing informed consent * R/R high-grade myeloid neoplasm following intensive induction chemotherapy; relapsed high-grade myeloid neoplasm: patients will be classified as relapsed if they have \>= 5% blasts after being in a complete remission (CR) following treatment for high-grade myeloid neoplasm; refractory high-grade myeloid neoplasm: patients may be classified as refractory if they have received at least one prior cycle of induction chemotherapy, whether with cladribine cytarabine mitoxantrone (GCLAM) or another regimen \*\* Patients may have received up to two courses of intensive induction chemotherapy during initial treatment prior to enrollment on this protocol; for example, patients who have received two courses of granulocyte colony stimulating factor (G-CSF) GCLAM (or similar) chemotherapy, with most recent high-dose cytarabine-containing chemotherapy \> 6 months ago and CR lasting \> 6 months, will be eligible for this protocol; regimens similar to GCLAM would include cytarabine at doses of 1g/m\^2 for at least 5 doses; examples of regimens similar to GCLAM would be GCLA, fludarabine cytarabine granulocyte (FLAG), and FLAG-idarubicin (ida); however, patients who received more than two courses of GCLAM (or similar) chemotherapy, or patients who received two courses of GCLAM and had CR lasting \< 6 months, would not be eligible * R/R high-grade myeloid neoplasm following less intensive induction chemotherapy. Patients who have received at least three cycles of treatment with a hypomethylating agent (HMA; such as azacitidine or decitabine) and still have \>= 10% blasts will be eligible for the study (they will be considered refractory); similarly, patients who have received three or more cycles of HMA therapy who have had a response (e.g., achieving CR with \< 5% blasts), but who then progress using standard definitions of relapse, will also be eligible (they will be considered relapsed) * Potentially eligible for reduced intensity conditioning based on known organ function (formal organ function testing may occur after consent) * Caregiver capable of providing post-HCT care * Written informed consent INCLUSION CRITERIA (TRANSPLANT) * Identified donor (see DONOR SELECTION below for further details) * Matched related or unrelated (one allele mismatch in HLA-A, B, or C OK) donor according to institutional standards * Unrelated volunteer donor who is mismatched with the recipient (i.e. 9/10 match) * Caregiver capable of providing post-HCT care, who will be present once induction therapy with filgrastim, cladribine, cytarabine, mitoxantrone hydrochloride (GCLAM) begins * Written informed consent for transplant * Either bone marrow or peripheral blood is allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant | Up to 60 days after start of chemotherapy | Success will be defined as enrollment of at least 30 patients with transplants occurring in 15 of these 30 (50%) within 60 days of enrollment or start of induction chemotherapy with G-CLAM, whichever is earlier. |
| Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant | 6 months after early allogeneic HCT on study | Success will be defined as observing a 40% of higher 6-month relapse-free survival among patients who received early transplant on study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | Approximately 84 days after early allogeneic HCT | Complete Remission (CR), defined as \<5% blasts in bone marrow with hematologic recovery (ANC\>1000/ul and platelets \>100,000/ml). CRi, defined as complete remission with insufficient hematologic recovery (ANC\<1000/ul or platelets\<100,000/ul). CRp, defined as complete remission but platelets \<100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria. Morphologic leukemia-free state (MLFS), defined as \<5% blasts in bone marrow with no hematologic recovery. Relapse, defined as \>5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease. |
| Relapse-free Survival (RFS) Among Patients Who Received Early Transplant | Up to 100 days post-transplant | Relapse-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. |
| Event-free Survival (EFS) Among Patients Who Received Early Transplant | Up to 100 days post-transplant | Event-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. Events included death, relapse, and grade 3-4 acute graft vs host disease. |
| Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant | Up to 100 days after induction day 1 | Overall survival among patients who did not receive early allogeneic HCT on study as estimated with the Kaplan-Meier method. |
| Acute Graft Versus Host Disease Among Patients Who Received Early Transplant | At day 100 | Acute graft versus host disease (graded II, III, or IV) among patients who received early allogeneic HCT on study. |
| Overall Survival (OS) Among Patients Who Received Early Transplant. | Up to 100 days post-transplant | Overall survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. |
| Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY | From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study) | Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of treatment-related mortality (TRM). This outcome measure is intended to report a predicted TRM score assessed at the time of feasibility evaluation. The TRM score is used to measure treatment-related mortality, or likelihood of death within 28 days of initiation of induction chemotherapy for patients with AML. The score is normalized from 0 to 100, so that a score of 0 demonstrates the patient has a very low likelihood of TRM and a score of 100 a very high likelihood of death. A calculation is used to predict TRM using age, performance status, if they have secondary AML, albumin, creatinine, platelet count, white blood cell count, and peripheral blood blast percentage. The higher the TRM score, the higher the risk of TRM. Calculator and table of relationship between TRM score and TRM probability found here: https://trmcalculator.fredhutch.org/. |
| Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER | From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study) | Patients who receive early transplant will be compared to those that don't using the Fisher's exact test for the categorical variables of gender. |
| Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE | From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study) | Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of age. |
| Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | Up to 12 months post-HCT | The amount of returned patient-reported outcome questionnaires will be summarized for each collection timepoint using percent collection from surviving patients for PRO timepoints. |
| Demonstrate the Feasibility of Collecting Resource Utilization Data for Trial Participants | Within the first year of induction chemotherapy on study | The amount of days of hospitalization (the major driver of costs within the first year) will be collected for resource utilization. |
| Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant | At day 100 | Treatment related mortality calculated among patients who received early allogeneic HCT on study vs patients who did not receive early transplant on study. |
| Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | Approximately 28 days after early allogeneic HCT | Complete Remission (CR), defined as \<5% blasts in bone marrow with hematologic recovery (ANC\>1000/ul and platelets \>100,000/ml). CRi, defined as complete remission with insufficient hematologic recovery (ANC\<1000/ul or platelets\<100,000/ul). CRp, defined as complete remission but platelets \<100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria. Morphologic leukemia-free state (MLFS), defined as \<5% blasts in bone marrow with no hematologic recovery. Relapse, defined as \>5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy, HCT) All patients enrolled received bridge chemotherapy prior to anticipated allogeneic hematopoietic cell transplantation (HCT). Patients received G-CLAM chemotherapy (consisting of G-CSF, mitoxantrone, cladribine, and cytarabine). HCT conditioning consisted of fludarabine and melphalan, with total body irradiation for patients over age 55 or with significant co-morbidities. HCT was to be received within 60 days of starting G-CLAM chemotherapy. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy, HCT) |
|---|---|
| Age, Customized | 56.5 years |
| Disease Status Refractory | 14 Participants |
| Disease Status Relapsed | 16 Participants |
| Duration of First Complete Remission | 2 Months |
| ELN 2017 Risk Stratification Adverse | 15 Participants |
| ELN 2017 Risk Stratification Favorable | 5 Participants |
| ELN 2017 Risk Stratification Intermediate | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| High-Grade Myeloid Diagnosis Acute myeloid leukemia (AML) | 29 Participants |
| High-Grade Myeloid Diagnosis Myelodysplastic syndrome excess blasts 2 (MDS EB-2) | 1 Participants |
| Prior Lines of Therapy | 2 Number of prior treatment regimens |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex/Gender, Customized Female | 18 Participants |
| Sex/Gender, Customized Male | 12 Participants |
| Treatment Related Mortality Score | 2.33 units on a scale (0-100) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 30 | 2 / 9 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 30 / 30 | 9 / 9 |
Outcome results
Primary
Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant
Success will be defined as enrollment of at least 30 patients with transplants occurring in 15 of these 30 (50%) within 60 days of enrollment or start of induction chemotherapy with G-CLAM, whichever is earlier.
Time frame: Up to 60 days after start of chemotherapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant | Received allogeneic HCT on study within 60 days (feasibility success) | 9 Participants |
| Treatment (Chemotherapy, HCT) | Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant | Did not receive allogeneic HCT on study within 60 days (feasibility failure) | 21 Participants |
Primary
Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant
Success will be defined as observing a 40% of higher 6-month relapse-free survival among patients who received early transplant on study.
Time frame: 6 months after early allogeneic HCT on study
Population: Nine subjects received allogeneic HCT on study, however one subject died shortly after HCT and was not including in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant | No relapse within 6 months post-HCT (feasibility success) | 6 Participants |
| Treatment (Chemotherapy, HCT) | Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant | Relapse within 6 months post-HCT (feasibility failure) | 2 Participants |
Secondary
Acute Graft Versus Host Disease Among Patients Who Received Early Transplant
Acute graft versus host disease (graded II, III, or IV) among patients who received early allogeneic HCT on study.
Time frame: At day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Acute Graft Versus Host Disease Among Patients Who Received Early Transplant | 0 Participants |
Secondary
Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants
The amount of returned patient-reported outcome questionnaires will be summarized for each collection timepoint using percent collection from surviving patients for PRO timepoints.
Time frame: Up to 12 months post-HCT
Population: The number analyzed in each of the rows below represent the patients alive at that timepoint who were due to complete a survey.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | Enrollment PROs returned | 27 Participants |
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | Post G-CLAM PROs returned | 23 Participants |
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | Pre-HCT PROs returned | 8 Participants |
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | 6 months post-HCT PROs returned | 4 Participants |
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants | 12 months post-HCT PROs returned | 3 Participants |
Secondary
Demonstrate the Feasibility of Collecting Resource Utilization Data for Trial Participants
The amount of days of hospitalization (the major driver of costs within the first year) will be collected for resource utilization.
Time frame: Within the first year of induction chemotherapy on study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Demonstrate the Feasibility of Collecting Resource Utilization Data for Trial Participants | 49 days |
Secondary
Event-free Survival (EFS) Among Patients Who Received Early Transplant
Event-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. Events included death, relapse, and grade 3-4 acute graft vs host disease.
Time frame: Up to 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Event-free Survival (EFS) Among Patients Who Received Early Transplant | 91 Percentage of participants |
Secondary
Event-free Survival (EFS) Among Patients Who Received Early Transplant
Event-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. Events included death, relapse, and grade 3-4 acute graft vs host disease.
Time frame: Up to 6 months post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Event-free Survival (EFS) Among Patients Who Received Early Transplant | 82 Percentage of participants |
Secondary
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE
Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of age.
Time frame: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE | 55 years |
| Did Not Receive Allogeneic HCT on Study | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE | 57 years |
p-value: 0.77Wilcoxon (Mann-Whitney)
Secondary
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER
Patients who receive early transplant will be compared to those that don't using the Fisher's exact test for the categorical variables of gender.
Time frame: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER | Male | 1 Participants |
| Treatment (Chemotherapy, HCT) | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER | Female | 8 Participants |
| Did Not Receive Allogeneic HCT on Study | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER | Male | 11 Participants |
| Did Not Receive Allogeneic HCT on Study | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER | Female | 10 Participants |
p-value: 0.049Fisher Exact
Secondary
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY
Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of treatment-related mortality (TRM). This outcome measure is intended to report a predicted TRM score assessed at the time of feasibility evaluation. The TRM score is used to measure treatment-related mortality, or likelihood of death within 28 days of initiation of induction chemotherapy for patients with AML. The score is normalized from 0 to 100, so that a score of 0 demonstrates the patient has a very low likelihood of TRM and a score of 100 a very high likelihood of death. A calculation is used to predict TRM using age, performance status, if they have secondary AML, albumin, creatinine, platelet count, white blood cell count, and peripheral blood blast percentage. The higher the TRM score, the higher the risk of TRM. Calculator and table of relationship between TRM score and TRM probability found here: https://trmcalculator.fredhutch.org/.
Time frame: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
Population: Only 18 of the 21 patients who did not receive an allogeneic hematopoietic peripheral blood stem cell within 60 days of bridge chemotherapy on study were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY | 2.15 units on a scale |
| Did Not Receive Allogeneic HCT on Study | Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY | 3.045 units on a scale |
p-value: 0.18Wilcoxon (Mann-Whitney)
Secondary
Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant
Overall survival among patients who did not receive early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 6 months after induction day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant | 62 Percentage of participants |
Secondary
Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant
Overall survival among patients who did not receive early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 100 days after induction day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant | 75 Percentage of participants |
Secondary
Overall Survival (OS) Among Patients Who Received Early Transplant.
Overall survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 6 months post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Overall Survival (OS) Among Patients Who Received Early Transplant. | 82 Percentage of participants |
Secondary
Overall Survival (OS) Among Patients Who Received Early Transplant.
Overall survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Overall Survival (OS) Among Patients Who Received Early Transplant. | 91 Percentage of participants |
Secondary
Relapse-free Survival (RFS) Among Patients Who Received Early Transplant
Relapse-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 6 months post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Relapse-free Survival (RFS) Among Patients Who Received Early Transplant | 82 Percentage of participants |
Secondary
Relapse-free Survival (RFS) Among Patients Who Received Early Transplant
Relapse-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method.
Time frame: Up to 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Relapse-free Survival (RFS) Among Patients Who Received Early Transplant | 91 Percentage of participants |
Secondary
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28
Complete Remission (CR), defined as \<5% blasts in bone marrow with hematologic recovery (ANC\>1000/ul and platelets \>100,000/ml). CRi, defined as complete remission with insufficient hematologic recovery (ANC\<1000/ul or platelets\<100,000/ul). CRp, defined as complete remission but platelets \<100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria. Morphologic leukemia-free state (MLFS), defined as \<5% blasts in bone marrow with no hematologic recovery. Relapse, defined as \>5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease.
Time frame: Approximately 28 days after early allogeneic HCT
Population: Nine subjects received allogeneic HCT on study, however one subject died shortly after HCT and was not including in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | CR with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | CR without MRD | 7 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | CRi with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | CRi without MRD | 1 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | MLFS with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | MLFS without MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28 | Relapse | 0 Participants |
Secondary
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84
Complete Remission (CR), defined as \<5% blasts in bone marrow with hematologic recovery (ANC\>1000/ul and platelets \>100,000/ml). CRi, defined as complete remission with insufficient hematologic recovery (ANC\<1000/ul or platelets\<100,000/ul). CRp, defined as complete remission but platelets \<100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria. Morphologic leukemia-free state (MLFS), defined as \<5% blasts in bone marrow with no hematologic recovery. Relapse, defined as \>5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease.
Time frame: Approximately 84 days after early allogeneic HCT
Population: Nine subjects received allogeneic HCT on study, however one subject died shortly after HCT and was not included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | CR with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | CR without MRD | 4 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | CRi with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | CRi without MRD | 2 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | MLFS with MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | MLFS without MRD | 0 Participants |
| Treatment (Chemotherapy, HCT) | Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84 | Relapse | 2 Participants |
Secondary
Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant
Treatment related mortality calculated among patients who received early allogeneic HCT on study vs patients who did not receive early transplant on study.
Time frame: At day 100
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, HCT) | Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant | 9 Percentage of participants |
| Did Not Receive Allogeneic HCT on Study | Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant | 23.8 Percentage of participants |
p-value: 0.18Wilcoxon (Mann-Whitney)