AML
Conditions
Keywords
AML, leukemia, myelogenous, myeloid, refractory
Brief summary
Open-label, multi-dose, single-arm, multi-center, Phase 1/2 study conducted in three segments: the Single Patient Dose Escalation Segment (complete), followed by the Multi-Patient Dose Escalation Segment (complete) and the Maximum Tolerated Dose and Schedule (MTDS) Expansion Cohort Segment (closed). Having characterized safety and determined the maximum tolerated dose and schedule, the primary objective of this study now is to assess the anti-neoplastic activity of flotetuzumab in patients with PIF/ER AML, as determined by the proportion of patients who achieve CR or CRh. Starting with Cycle 2, patients who are benefiting from flotetuzumab may receive up to a maximum of 8 cycles of treatment. Patients will receive daily increasing doses of flotetuzumab for the first week of Cycle 1 (Lead-In Dosing) followed by 3 weeks of continuous intravenous infusion at a the assigned dose. Subsequent cycles are each 4 weeks of continuous infusion at the assigned dose. Dosing may continue for up to 8 cycles. Follow up visits may continue for 6 months after treatment is discontinued.
Interventions
BIOLOGICALFlotetuzumab 3 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
BIOLOGICALFlotetuzumab 10 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 30 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 100 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
BIOLOGICALFlotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
BIOLOGICALFlotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
DRUGRuxolitinib
Oral inhibitor of JAK kinase
BIOLOGICALFlotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of primary or secondary AML \[any subtype except acute promyelocytic leukemia (APL)\] according to World Health Organization (WHO) classification * Patients with AML must meet one of the following criteria, a or b: 1. Primary Induction Failure (PIF) AML, defined as disease refractory to either, i or ii: * i. An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. Examples include but are not limited to: 1 cycle of high dose cytarabine (HiDAC) containing regimen, 1 cycle of liposomal cytarabine and daunorubicin, 2 cycles of standard dose cytarabine containing regimen * ii. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens: i ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine, or ii ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy 2. Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration \< 6 months * Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): up to 2 induction (induction, re-induction) or 1 induction plus/minus 1 consolidation attempt, followed by a maximum of 1 salvage/re-induction attempt. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * Life expectancy of at least 4 weeks * Peripheral blast count \</= 20,000/mm3 at the time of first dose * Acceptable laboratory parameters and adequate organ reserve
Exclusion criteria
* History of allogeneic stem cell transplantation * Prior treatment with an anti-CD123-directed agent * Need for concurrent other cytoreductive chemotherapy * Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation) * Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. * Antitumor therapy or investigational agent within 14 days or 5 half-lives of Cycle 1 Day 1. * Requirement, at the time of study entry, for concurrent steroids \> 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, otic preparations, nasal spray or ophthalmic solution * Use of immunosuppressant medications in the 2 weeks prior to Cycle 1 Day 1 * Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to Cycle 1 Day 1 * Known central nervous system (CNS) leukemia * Active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection), * Known human immunodeficiency virus infection, unless all of the following criteria are met: CD4+ count ≥ 350 cells/μL, undetectable viral load, and receiving highly active antiretroviral therapy. * Known, active, history of or current acute or chronic hepatitis B or C virus (HBV) infection (as evidenced by detectable HBV surface antigen and HBV DNA ≥ 500 IU/mL), * History of hepatitis C virus (HCV) infection, unless the infection has been treated and cured, * Active SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing for ongoing infection should follow local clinical practice guidelines/standards. Participants with a positive test result for ongoing SARS-CoV-2 infection, known asymptomatic infection, or suspected infection are excluded unless or until asymptomatic and with subsequent negative SARS-CoV-2 laboratory test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Based on CR or CRh Rate | up to 14 months | Proportion of patients achieving a best response of CR (morphologic CR \[mCR\], cytogenetic CR \[CRc\], molecular CR \[CRm\], or CRh per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR Rate | up to 14 months | Proportion of patients achieving a best response of CR (morphologic CR \[mCR\], cytogenetic CR \[CRc\], or molecular CR \[CRm\] per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery. |
| CRh Rate | up to 14 months | Proportion of patients achieving a best response of CRh per Interworking Group AML response criteria. CRh is defined as: CR with partial hematologic recovery. |
| Overall Response Rate | up to 14 months | Proportion of patients achieving a best response of CR, CRh, CRi, MLFS or partial response per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery. |
| HSCT Rate | up to 8 months | Rate of successful hematopoietic stem cell transplantation (HSCT) after the start flotetuzumab treatment and before subsequent therapy. |
| Occurrence of Dose Limiting Toxicity | Cycle 1 of a 28 day cycle. | Maximum Tolerated Dose/Schedule: the MTDS is defined as the highest dose/schedule administered during any Cohort in the study at which the incidence of DLT is \< 33% during the first cycle of MGD006 treatment. |
| Occurrence of Adverse Events (AEs) | up to 9 months | Cycle 1 through end of treatment |
| Occurrence of Serious Adverse Events (SAEs) | up to 9 months | — |
| Participants With Anti-drug Antibodies | Study Day 1, then every 28 days through 28-days after the last dose (up to 8 months) | Occurrence of anti-drug antibody |
| Number of Patients With Infusion Related Reaction (IRR) | During study drug administration (up to 8 months) | Determine safety and efficacy of tocilizumab in the treatment of IRR/CRS as measured by incidence of IRR/CRS |
| Number of Patients With Cytokine Release Syndrome (CRS) | up to 9 months | — |
| Overall Complete Response Rate | up to 14 months | Rate of CR + CRh + CRi (CR with incomplete blood cell recovery \[CR with incomplete neutrophil {CRn}or platelet recovery {CRp}\]) + MLFS (morphologic leukemia-free state) |
| Post-baseline Transfusion Independence Rate | 56 days | The number of patients who were transfusion-dependent at baseline and did not receive transfusions during any consecutive 56-day period will be calculated. The number of patients who are transfusion independent at baseline and remain independent during any 56-day post-baseline period will also be calculated. |
| Number of Patients Alive at 6 Months | 6 months | — |
| Event-free Survival | Up to 2 years | Time from the first dose of study drug until date of evidence of primary refractory disease to flotetuzumab, relapse from CR, CRh or CRi, or death from any cause, whichever occurs first. |
| Mortality Rate | Throughout the study, up to 3 years. | number of deaths from any cause within 30, 60, 90, or 180 days of first dose of study drug |
| Number of Patients Alive at 12 Months | 1 year | Number of patients alive at 1 year from first dose of study drug |
| Median Time to Response | up to 14 months | Time from first dose of study drug to first CR, CRh, CRi, or MLFS |
| Duration of Response of Patients With CR or CRh | Up to 2 years | Time of initial documentation of response to the time of disease relapse or death due to any cause, whichever occurs first. |
| Overall Survival | Up to 2 years | Time from first dose to death from any cause |
| Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge | up to 8 months | Initial dosing procedures were performed as a hospital inpatient. Incidence rate of hospitalization after discharge from the hospital will be calculated |
| Duration of Hospitalization for Patients in the Expansion Cohort | up to 8 months | Duration of hospitalization will be characterized after discharge from initial dosing will be characterized |
| Maximum Serum Concentration of Flotetuzumab | Study day 1, then every 28 days and 28 days after the last dose (up to 8 months) | Measure the pharmacokinetics (PK) of flotetuzumab |
Countries
France, Germany, Israel, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 0-a Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off | 1 |
| Cohort 0-b Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off | 4 |
| Cohort 0-c Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off | 5 |
| Cohort 0-d Flotetuzumab 100 ng/kg/day, 4 days on and 3 days off | 4 |
| Cohort 1 Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after lead-in dose | 3 |
| Cohort 2 Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after lead-in dose | 4 |
| Cohort 2a Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after multistep lead-in dose | 6 |
| Cohort 3 Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multistep lead-in dose | 6 |
| Cohort 6 Flotetuzumab 300 ng/kg/day, continuous infusion, after multistep lead-in dose | 6 |
| Cohort 7 Flotetuzumab 500 ng/kg/day, continuous infusion, after multistep lead-in dose | 5 |
| Cohort 8 Flotetuzumab 700 ng/kg/day, continuous infusion, after multistep lead-in dose | 3 |
| MTD Expansion Flotetuzumab 500 ng/kg/day, continuous infusion, after multistep lead-in dose | 185 |
| MTD Expansion With Ruxolitinib Flotetuzumab 500 ng/kg/day, continuous infusion, after multistep lead-in dose Ruxolitinib: Oral inhibitor of JAK kinase | 12 |
| Total | 244 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 |
| Overall Study | Death | 0 | 3 | 3 | 4 | 1 | 2 | 6 | 6 | 4 | 5 | 3 | 143 | 12 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 29 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Cohort 0-a | Cohort 0-b | Cohort 0-c | Cohort 0-d | Cohort 1 | Cohort 2 | Cohort 2a | Cohort 3 | Cohort 6 | Cohort 7 | Cohort 8 | MTD Expansion | MTD Expansion With Ruxolitinib | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52 years | 59.3 years STANDARD_DEVIATION 21.28 | 56.4 years STANDARD_DEVIATION 17.1 | 71.8 years STANDARD_DEVIATION 16.54 | 58.3 years STANDARD_DEVIATION 14.5 | 67.3 years STANDARD_DEVIATION 11.64 | 53.0 years STANDARD_DEVIATION 11.33 | 73.5 years STANDARD_DEVIATION 5.92 | 64.0 years STANDARD_DEVIATION 10.81 | 61.2 years STANDARD_DEVIATION 20.17 | 70.0 years STANDARD_DEVIATION 8.19 | 58.3 years STANDARD_DEVIATION 14.29 | 65.7 years STANDARD_DEVIATION 12.02 | 59.5 years STANDARD_DEVIATION 14.36 |
| Age, Customized 18 - 65 | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 121 Participants | 6 Participants | 151 Participants |
| Age, Customized 66 - 75 | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 53 Participants | 3 Participants | 69 Participants |
| Age, Customized >75 | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 11 Participants | 3 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 15 Participants | 0 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 2 Participants | 145 Participants | 12 Participants | 200 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 25 Participants | 0 Participants | 29 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 12 Participants | 0 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 14 Participants | 3 Participants | 22 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 21 Participants | 0 Participants | 21 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 4 Participants | 5 Participants | 3 Participants | 133 Participants | 9 Participants | 183 Participants |
| Region of Enrollment France | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 26 participants | 0 participants | 28 participants |
| Region of Enrollment Germany | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 15 participants | 0 participants | 17 participants |
| Region of Enrollment Italy | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants | 8 participants | 0 participants | 12 participants |
| Region of Enrollment Netherlands | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 9 participants | 0 participants | 10 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment United Kingdom | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 5 participants | 0 participants | 5 participants |
| Region of Enrollment United States | 1 participants | 4 participants | 5 participants | 4 participants | 3 participants | 4 participants | 4 participants | 4 participants | 5 participants | 3 participants | 1 participants | 120 participants | 12 participants | 170 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 85 Participants | 4 Participants | 109 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 100 Participants | 8 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 3 / 4 | 3 / 5 | 4 / 4 | 2 / 3 | 2 / 4 | 6 / 6 | 6 / 6 | 5 / 6 | 5 / 5 | 3 / 3 | 144 / 185 | 12 / 12 |
| other Total, other adverse events | 1 / 1 | 4 / 4 | 5 / 5 | 4 / 4 | 3 / 3 | 4 / 4 | 6 / 6 | 6 / 6 | 6 / 6 | 5 / 5 | 3 / 3 | 185 / 185 | 12 / 12 |
| serious Total, serious adverse events | 0 / 1 | 1 / 4 | 0 / 5 | 2 / 4 | 1 / 3 | 2 / 4 | 2 / 6 | 1 / 6 | 0 / 6 | 3 / 5 | 1 / 3 | 100 / 185 | 6 / 12 |
Outcome results
Primary
Efficacy Based on CR or CRh Rate
Proportion of patients achieving a best response of CR (morphologic CR \[mCR\], cytogenetic CR \[CRc\], molecular CR \[CRm\], or CRh per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery.
Time frame: up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 0-b | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 0-c | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 0-d | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 1 | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 2 | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 2a | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 3 | Efficacy Based on CR or CRh Rate | 1 Participants |
| Cohort 6 | Efficacy Based on CR or CRh Rate | 0 Participants |
| Cohort 7 | Efficacy Based on CR or CRh Rate | 1 Participants |
| Cohort 8 | Efficacy Based on CR or CRh Rate | 0 Participants |
| MTD Expansion | Efficacy Based on CR or CRh Rate | 16 Participants |
| MTD Expansion With Ruxolitinib | Efficacy Based on CR or CRh Rate | 4 Participants |
Secondary
CRh Rate
Proportion of patients achieving a best response of CRh per Interworking Group AML response criteria. CRh is defined as: CR with partial hematologic recovery.
Time frame: up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | CRh Rate | 0 Participants |
| Cohort 0-b | CRh Rate | 0 Participants |
| Cohort 0-c | CRh Rate | 0 Participants |
| Cohort 0-d | CRh Rate | 0 Participants |
| Cohort 1 | CRh Rate | 0 Participants |
| Cohort 2 | CRh Rate | 0 Participants |
| Cohort 2a | CRh Rate | 0 Participants |
| Cohort 3 | CRh Rate | 0 Participants |
| Cohort 6 | CRh Rate | 0 Participants |
| Cohort 7 | CRh Rate | 0 Participants |
| Cohort 8 | CRh Rate | 0 Participants |
| MTD Expansion | CRh Rate | 3 Participants |
| MTD Expansion With Ruxolitinib | CRh Rate | 2 Participants |
Secondary
CR Rate
Proportion of patients achieving a best response of CR (morphologic CR \[mCR\], cytogenetic CR \[CRc\], or molecular CR \[CRm\] per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery.
Time frame: up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | CR Rate | 0 Participants |
| Cohort 0-b | CR Rate | 0 Participants |
| Cohort 0-c | CR Rate | 0 Participants |
| Cohort 0-d | CR Rate | 0 Participants |
| Cohort 1 | CR Rate | 0 Participants |
| Cohort 2 | CR Rate | 0 Participants |
| Cohort 2a | CR Rate | 0 Participants |
| Cohort 3 | CR Rate | 1 Participants |
| Cohort 6 | CR Rate | 0 Participants |
| Cohort 7 | CR Rate | 1 Participants |
| Cohort 8 | CR Rate | 0 Participants |
| MTD Expansion | CR Rate | 13 Participants |
| MTD Expansion With Ruxolitinib | CR Rate | 2 Participants |
Secondary
Duration of Hospitalization for Patients in the Expansion Cohort
Duration of hospitalization will be characterized after discharge from initial dosing will be characterized
Time frame: up to 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Duration of Hospitalization for Patients in the Expansion Cohort | NA Participants |
Secondary
Duration of Response of Patients With CR or CRh
Time of initial documentation of response to the time of disease relapse or death due to any cause, whichever occurs first.
Time frame: Up to 2 years
Population: Analysis is based on the number of participants who had a CR or CRh as reported in Outcome Measure 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 | Duration of Response of Patients With CR or CRh | 4.0 Months | — |
| Cohort 7 | Duration of Response of Patients With CR or CRh | 2.3 Months | — |
| MTD Expansion | Duration of Response of Patients With CR or CRh | 1.4 Months | Standard Deviation 1.04 |
| MTD Expansion With Ruxolitinib | Duration of Response of Patients With CR or CRh | 1.1 Months | Standard Deviation 1.56 |
Secondary
Event-free Survival
Time from the first dose of study drug until date of evidence of primary refractory disease to flotetuzumab, relapse from CR, CRh or CRi, or death from any cause, whichever occurs first.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 0-a | Event-free Survival | NA months |
| Cohort 0-b | Event-free Survival | NA months |
| Cohort 0-c | Event-free Survival | NA months |
| Cohort 0-d | Event-free Survival | NA months |
| Cohort 1 | Event-free Survival | NA months |
| Cohort 2 | Event-free Survival | NA months |
| Cohort 2a | Event-free Survival | NA months |
| Cohort 3 | Event-free Survival | NA months |
| Cohort 6 | Event-free Survival | NA months |
| Cohort 7 | Event-free Survival | NA months |
| Cohort 8 | Event-free Survival | NA months |
| MTD Expansion | Event-free Survival | NA months |
| MTD Expansion With Ruxolitinib | Event-free Survival | NA months |
Secondary
HSCT Rate
Rate of successful hematopoietic stem cell transplantation (HSCT) after the start flotetuzumab treatment and before subsequent therapy.
Time frame: up to 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | HSCT Rate | 0 Participants |
| Cohort 0-b | HSCT Rate | 0 Participants |
| Cohort 0-c | HSCT Rate | 0 Participants |
| Cohort 0-d | HSCT Rate | 0 Participants |
| Cohort 1 | HSCT Rate | 0 Participants |
| Cohort 2 | HSCT Rate | 0 Participants |
| Cohort 2a | HSCT Rate | 0 Participants |
| Cohort 3 | HSCT Rate | 0 Participants |
| Cohort 6 | HSCT Rate | 0 Participants |
| Cohort 7 | HSCT Rate | 0 Participants |
| Cohort 8 | HSCT Rate | 0 Participants |
| MTD Expansion | HSCT Rate | 10 Participants |
| MTD Expansion With Ruxolitinib | HSCT Rate | 1 Participants |
Secondary
Maximum Serum Concentration of Flotetuzumab
Measure the pharmacokinetics (PK) of flotetuzumab
Time frame: Study day 1, then every 28 days and 28 days after the last dose (up to 8 months)
Population: The PK analysis was conducted for patients receiving 10, 30, 100, 300, and 500 ng/kg/day. The study drug was administered as continuous IV dosing. Due to the short half-life, Cmax is not influenced by drug administration schedule. The data for all participants treated at a dose, regardless of schedule, were analyzed together. Specimens were collected and individually analyzed for concentrations only in the 700 ng/kg/day, no PK parameters were derived for this dose group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 0-a | Maximum Serum Concentration of Flotetuzumab | 16.1 pg/mL |
| Cohort 0-b | Maximum Serum Concentration of Flotetuzumab | 34.5 pg/mL |
| Cohort 0-c | Maximum Serum Concentration of Flotetuzumab | 82.8 pg/mL |
| Cohort 0-d | Maximum Serum Concentration of Flotetuzumab | 177 pg/mL |
| Cohort 1 | Maximum Serum Concentration of Flotetuzumab | 185 pg/mL |
Secondary
Median Time to Response
Time from first dose of study drug to first CR, CRh, CRi, or MLFS
Time frame: up to 14 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 0-a | Median Time to Response | NA months |
| Cohort 0-b | Median Time to Response | NA months |
| Cohort 0-c | Median Time to Response | NA months |
| Cohort 0-d | Median Time to Response | NA months |
| Cohort 1 | Median Time to Response | NA months |
| Cohort 2 | Median Time to Response | NA months |
| Cohort 2a | Median Time to Response | NA months |
| Cohort 3 | Median Time to Response | NA months |
| Cohort 6 | Median Time to Response | NA months |
| Cohort 7 | Median Time to Response | NA months |
| Cohort 8 | Median Time to Response | NA months |
| MTD Expansion | Median Time to Response | NA months |
| MTD Expansion With Ruxolitinib | Median Time to Response | NA months |
Secondary
Mortality Rate
number of deaths from any cause within 30, 60, 90, or 180 days of first dose of study drug
Time frame: Throughout the study, up to 3 years.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 0-a | Mortality Rate | unknown | 0 Participants |
| Cohort 0-a | Mortality Rate | Mortality at 61-90 days | 0 Participants |
| Cohort 0-a | Mortality Rate | Mortality at 91- >180 days | 1 Participants |
| Cohort 0-a | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 0-a | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 0-b | Mortality Rate | Mortality at 91- >180 days | 2 Participants |
| Cohort 0-b | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 0-b | Mortality Rate | unknown | 0 Participants |
| Cohort 0-b | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 0-b | Mortality Rate | Mortality at 31-60 days | 1 Participants |
| Cohort 0-c | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 0-c | Mortality Rate | Mortality at 0-30 days | 1 Participants |
| Cohort 0-c | Mortality Rate | unknown | 1 Participants |
| Cohort 0-c | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 0-c | Mortality Rate | Mortality at 91- >180 days | 2 Participants |
| Cohort 0-d | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 0-d | Mortality Rate | Mortality at 61-90 days | 0 Participants |
| Cohort 0-d | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 0-d | Mortality Rate | Mortality at 91- >180 days | 4 Participants |
| Cohort 0-d | Mortality Rate | unknown | 0 Participants |
| Cohort 1 | Mortality Rate | unknown | 1 Participants |
| Cohort 1 | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 1 | Mortality Rate | Mortality at 31-60 days | 1 Participants |
| Cohort 1 | Mortality Rate | Mortality at 91- >180 days | 0 Participants |
| Cohort 1 | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 2 | Mortality Rate | unknown | 2 Participants |
| Cohort 2 | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 2 | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 2 | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 2 | Mortality Rate | Mortality at 91- >180 days | 1 Participants |
| Cohort 2a | Mortality Rate | unknown | 0 Participants |
| Cohort 2a | Mortality Rate | Mortality at 0-30 days | 1 Participants |
| Cohort 2a | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 2a | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 2a | Mortality Rate | Mortality at 91- >180 days | 4 Participants |
| Cohort 3 | Mortality Rate | Mortality at 31-60 days | 1 Participants |
| Cohort 3 | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 3 | Mortality Rate | unknown | 0 Participants |
| Cohort 3 | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 3 | Mortality Rate | Mortality at 91- >180 days | 4 Participants |
| Cohort 6 | Mortality Rate | Mortality at 61-90 days | 0 Participants |
| Cohort 6 | Mortality Rate | Mortality at 31-60 days | 0 Participants |
| Cohort 6 | Mortality Rate | Mortality at 91- >180 days | 4 Participants |
| Cohort 6 | Mortality Rate | Mortality at 0-30 days | 1 Participants |
| Cohort 6 | Mortality Rate | unknown | 1 Participants |
| Cohort 7 | Mortality Rate | Mortality at 31-60 days | 1 Participants |
| Cohort 7 | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 7 | Mortality Rate | Mortality at 0-30 days | 1 Participants |
| Cohort 7 | Mortality Rate | unknown | 0 Participants |
| Cohort 7 | Mortality Rate | Mortality at 91- >180 days | 2 Participants |
| Cohort 8 | Mortality Rate | Mortality at 0-30 days | 0 Participants |
| Cohort 8 | Mortality Rate | unknown | 0 Participants |
| Cohort 8 | Mortality Rate | Mortality at 91- >180 days | 1 Participants |
| Cohort 8 | Mortality Rate | Mortality at 61-90 days | 1 Participants |
| Cohort 8 | Mortality Rate | Mortality at 31-60 days | 1 Participants |
| MTD Expansion | Mortality Rate | Mortality at 0-30 days | 23 Participants |
| MTD Expansion | Mortality Rate | unknown | 42 Participants |
| MTD Expansion | Mortality Rate | Mortality at 61-90 days | 19 Participants |
| MTD Expansion | Mortality Rate | Mortality at 91- >180 days | 67 Participants |
| MTD Expansion | Mortality Rate | Mortality at 31-60 days | 34 Participants |
| MTD Expansion With Ruxolitinib | Mortality Rate | Mortality at 0-30 days | 2 Participants |
| MTD Expansion With Ruxolitinib | Mortality Rate | Mortality at 91- >180 days | 6 Participants |
| MTD Expansion With Ruxolitinib | Mortality Rate | Mortality at 31-60 days | 3 Participants |
| MTD Expansion With Ruxolitinib | Mortality Rate | unknown | 0 Participants |
| MTD Expansion With Ruxolitinib | Mortality Rate | Mortality at 61-90 days | 1 Participants |
Secondary
Number of Patients Alive at 12 Months
Number of patients alive at 1 year from first dose of study drug
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Number of Patients Alive at 12 Months | 1 Participants |
| Cohort 0-b | Number of Patients Alive at 12 Months | 1 Participants |
| Cohort 0-c | Number of Patients Alive at 12 Months | 1 Participants |
| Cohort 0-d | Number of Patients Alive at 12 Months | 0 Participants |
| Cohort 1 | Number of Patients Alive at 12 Months | 0 Participants |
| Cohort 2 | Number of Patients Alive at 12 Months | 0 Participants |
| Cohort 2a | Number of Patients Alive at 12 Months | 0 Participants |
| Cohort 3 | Number of Patients Alive at 12 Months | 2 Participants |
| Cohort 6 | Number of Patients Alive at 12 Months | 1 Participants |
| Cohort 7 | Number of Patients Alive at 12 Months | 0 Participants |
| Cohort 8 | Number of Patients Alive at 12 Months | 1 Participants |
| MTD Expansion | Number of Patients Alive at 12 Months | 16 Participants |
| MTD Expansion With Ruxolitinib | Number of Patients Alive at 12 Months | 3 Participants |
Secondary
Number of Patients Alive at 6 Months
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Number of Patients Alive at 6 Months | 1 Participants |
| Cohort 0-b | Number of Patients Alive at 6 Months | 2 Participants |
| Cohort 0-c | Number of Patients Alive at 6 Months | 2 Participants |
| Cohort 0-d | Number of Patients Alive at 6 Months | 3 Participants |
| Cohort 1 | Number of Patients Alive at 6 Months | 0 Participants |
| Cohort 2 | Number of Patients Alive at 6 Months | 0 Participants |
| Cohort 2a | Number of Patients Alive at 6 Months | 2 Participants |
| Cohort 3 | Number of Patients Alive at 6 Months | 2 Participants |
| Cohort 6 | Number of Patients Alive at 6 Months | 2 Participants |
| Cohort 7 | Number of Patients Alive at 6 Months | 1 Participants |
| Cohort 8 | Number of Patients Alive at 6 Months | 1 Participants |
| MTD Expansion | Number of Patients Alive at 6 Months | 42 Participants |
| MTD Expansion With Ruxolitinib | Number of Patients Alive at 6 Months | 6 Participants |
Secondary
Number of Patients With Cytokine Release Syndrome (CRS)
Time frame: up to 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 0-b | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 0-c | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 0-d | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 1 | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 2 | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 2a | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 3 | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 6 | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| Cohort 7 | Number of Patients With Cytokine Release Syndrome (CRS) | 1 Participants |
| Cohort 8 | Number of Patients With Cytokine Release Syndrome (CRS) | 0 Participants |
| MTD Expansion | Number of Patients With Cytokine Release Syndrome (CRS) | 107 Participants |
| MTD Expansion With Ruxolitinib | Number of Patients With Cytokine Release Syndrome (CRS) | 4 Participants |
Secondary
Number of Patients With Infusion Related Reaction (IRR)
Determine safety and efficacy of tocilizumab in the treatment of IRR/CRS as measured by incidence of IRR/CRS
Time frame: During study drug administration (up to 8 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Number of Patients With Infusion Related Reaction (IRR) | 1 Participants |
| Cohort 0-b | Number of Patients With Infusion Related Reaction (IRR) | 3 Participants |
| Cohort 0-c | Number of Patients With Infusion Related Reaction (IRR) | 3 Participants |
| Cohort 0-d | Number of Patients With Infusion Related Reaction (IRR) | 3 Participants |
| Cohort 1 | Number of Patients With Infusion Related Reaction (IRR) | 3 Participants |
| Cohort 2 | Number of Patients With Infusion Related Reaction (IRR) | 3 Participants |
| Cohort 2a | Number of Patients With Infusion Related Reaction (IRR) | 5 Participants |
| Cohort 3 | Number of Patients With Infusion Related Reaction (IRR) | 6 Participants |
| Cohort 6 | Number of Patients With Infusion Related Reaction (IRR) | 5 Participants |
| Cohort 7 | Number of Patients With Infusion Related Reaction (IRR) | 5 Participants |
| Cohort 8 | Number of Patients With Infusion Related Reaction (IRR) | 2 Participants |
| MTD Expansion | Number of Patients With Infusion Related Reaction (IRR) | 78 Participants |
| MTD Expansion With Ruxolitinib | Number of Patients With Infusion Related Reaction (IRR) | 8 Participants |
Secondary
Occurrence of Adverse Events (AEs)
Cycle 1 through end of treatment
Time frame: up to 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Occurrence of Adverse Events (AEs) | 1 Participants |
| Cohort 0-b | Occurrence of Adverse Events (AEs) | 4 Participants |
| Cohort 0-c | Occurrence of Adverse Events (AEs) | 5 Participants |
| Cohort 0-d | Occurrence of Adverse Events (AEs) | 4 Participants |
| Cohort 1 | Occurrence of Adverse Events (AEs) | 3 Participants |
| Cohort 2 | Occurrence of Adverse Events (AEs) | 4 Participants |
| Cohort 2a | Occurrence of Adverse Events (AEs) | 6 Participants |
| Cohort 3 | Occurrence of Adverse Events (AEs) | 6 Participants |
| Cohort 6 | Occurrence of Adverse Events (AEs) | 6 Participants |
| Cohort 7 | Occurrence of Adverse Events (AEs) | 5 Participants |
| Cohort 8 | Occurrence of Adverse Events (AEs) | 3 Participants |
| MTD Expansion | Occurrence of Adverse Events (AEs) | 185 Participants |
| MTD Expansion With Ruxolitinib | Occurrence of Adverse Events (AEs) | 12 Participants |
Secondary
Occurrence of Dose Limiting Toxicity
Maximum Tolerated Dose/Schedule: the MTDS is defined as the highest dose/schedule administered during any Cohort in the study at which the incidence of DLT is \< 33% during the first cycle of MGD006 treatment.
Time frame: Cycle 1 of a 28 day cycle.
Population: DLT were reported for dose escalation cohorts only (cohort 0-8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 0-b | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 0-c | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 0-d | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 1 | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 2 | Occurrence of Dose Limiting Toxicity | 1 Participants |
| Cohort 2a | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 3 | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 6 | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 7 | Occurrence of Dose Limiting Toxicity | 0 Participants |
| Cohort 8 | Occurrence of Dose Limiting Toxicity | 0 Participants |
Secondary
Occurrence of Serious Adverse Events (SAEs)
Time frame: up to 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Occurrence of Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 0-b | Occurrence of Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 0-c | Occurrence of Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 0-d | Occurrence of Serious Adverse Events (SAEs) | 3 Participants |
| Cohort 1 | Occurrence of Serious Adverse Events (SAEs) | 1 Participants |
| Cohort 2 | Occurrence of Serious Adverse Events (SAEs) | 2 Participants |
| Cohort 2a | Occurrence of Serious Adverse Events (SAEs) | 2 Participants |
| Cohort 3 | Occurrence of Serious Adverse Events (SAEs) | 1 Participants |
| Cohort 6 | Occurrence of Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 7 | Occurrence of Serious Adverse Events (SAEs) | 3 Participants |
| Cohort 8 | Occurrence of Serious Adverse Events (SAEs) | 1 Participants |
| MTD Expansion | Occurrence of Serious Adverse Events (SAEs) | 100 Participants |
| MTD Expansion With Ruxolitinib | Occurrence of Serious Adverse Events (SAEs) | 6 Participants |
Secondary
Overall Complete Response Rate
Rate of CR + CRh + CRi (CR with incomplete blood cell recovery \[CR with incomplete neutrophil {CRn}or platelet recovery {CRp}\]) + MLFS (morphologic leukemia-free state)
Time frame: up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Overall Complete Response Rate | 0 Participants |
| Cohort 0-b | Overall Complete Response Rate | 0 Participants |
| Cohort 0-c | Overall Complete Response Rate | 0 Participants |
| Cohort 0-d | Overall Complete Response Rate | 0 Participants |
| Cohort 1 | Overall Complete Response Rate | 0 Participants |
| Cohort 2 | Overall Complete Response Rate | 0 Participants |
| Cohort 2a | Overall Complete Response Rate | 0 Participants |
| Cohort 3 | Overall Complete Response Rate | 1 Participants |
| Cohort 6 | Overall Complete Response Rate | 0 Participants |
| Cohort 7 | Overall Complete Response Rate | 1 Participants |
| Cohort 8 | Overall Complete Response Rate | 1 Participants |
| MTD Expansion | Overall Complete Response Rate | 27 Participants |
| MTD Expansion With Ruxolitinib | Overall Complete Response Rate | 4 Participants |
Secondary
Overall Response Rate
Proportion of patients achieving a best response of CR, CRh, CRi, MLFS or partial response per Interworking Group AML response criteria. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery.
Time frame: up to 14 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Overall Response Rate | 0 Participants |
| Cohort 0-b | Overall Response Rate | 0 Participants |
| Cohort 0-c | Overall Response Rate | 0 Participants |
| Cohort 0-d | Overall Response Rate | 0 Participants |
| Cohort 1 | Overall Response Rate | 0 Participants |
| Cohort 2 | Overall Response Rate | 1 Participants |
| Cohort 2a | Overall Response Rate | 1 Participants |
| Cohort 3 | Overall Response Rate | 1 Participants |
| Cohort 6 | Overall Response Rate | 0 Participants |
| Cohort 7 | Overall Response Rate | 2 Participants |
| Cohort 8 | Overall Response Rate | 1 Participants |
| MTD Expansion | Overall Response Rate | 35 Participants |
| MTD Expansion With Ruxolitinib | Overall Response Rate | 4 Participants |
Secondary
Overall Survival
Time from first dose to death from any cause
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 0-a | Overall Survival | NA months |
| Cohort 0-b | Overall Survival | NA months |
| Cohort 0-c | Overall Survival | NA months |
| Cohort 0-d | Overall Survival | NA months |
| Cohort 1 | Overall Survival | NA months |
| Cohort 2 | Overall Survival | NA months |
| Cohort 2a | Overall Survival | NA months |
| Cohort 3 | Overall Survival | NA months |
| Cohort 6 | Overall Survival | NA months |
| Cohort 7 | Overall Survival | NA months |
| Cohort 8 | Overall Survival | NA months |
| MTD Expansion | Overall Survival | NA months |
| MTD Expansion With Ruxolitinib | Overall Survival | NA months |
Secondary
Participants With Anti-drug Antibodies
Occurrence of anti-drug antibody
Time frame: Study Day 1, then every 28 days through 28-days after the last dose (up to 8 months)
Population: Participants were analyzed for the development of ADA regardless of dose level. Presence or absence of ADA is not related to dose level. The relevant information is the change from one status (positive, negative, or not tested) to a different status.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 0-a | Participants With Anti-drug Antibodies | Not tested at baseline, not tested on study | 144 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Not tested at baseline, all negative on study | 4 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Not tested at baseline, at least 1 positive on study | 0 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Negative at baseline, not tested on study | 25 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Negative at baseline, all negative on study | 70 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Negative at baseline, at least 1 positive on study | 1 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Positive at baseline, not tested on study | 0 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Positive at baseline, all negative on study | 0 Participants |
| Cohort 0-a | Participants With Anti-drug Antibodies | Positive at baseline, at least 1 positive on study | 0 Participants |
Secondary
Post-baseline Transfusion Independence Rate
The number of patients who were transfusion-dependent at baseline and did not receive transfusions during any consecutive 56-day period will be calculated. The number of patients who are transfusion independent at baseline and remain independent during any 56-day post-baseline period will also be calculated.
Time frame: 56 days
Population: No data was collected regarding transfusion dependency status at baseline or post-baseline.
Secondary
Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge
Initial dosing procedures were performed as a hospital inpatient. Incidence rate of hospitalization after discharge from the hospital will be calculated
Time frame: up to 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 0-a | Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge | NA Participants |