Relapsed Acute Myeloid Leukemia
Conditions
Brief summary
The investigators hypothesize that flotetuzumab for relapsed AML following allo-HCT will be safe, tolerable and may facilitate preferential immune effector cell retargeting of leukemic cells resulting in improved patient outcomes. Furthermore, administration of a donor lymphocyte infusion (DLI) (if available) in combination with flotetuzumab will be safe, tolerable and may provide additional therapeutic efficacy.
Interventions
DRUGFlotetuzumab
Will be provided by MacroGenics Inc.
PROCEDUREDonor lymphocyte infusion
DLI represents a non-specific form of adoptive cell therapy which involves infusion of a pool of allogeneic immune cells, including CD4+ T cells, CD8+ T cells, regulatory T cells (T Regs), natural killer (NK) cells and professional antigen presenting cells.
Sponsors
MacroGenics
National Cancer Institute (NCI)
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Histologically or cytologically confirmed relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), including any AML subtype, except acute promyelocytic leukemia (APL), and including AML that has evolved from a previous MDS or MPN. * Patients must have peripheral blast count ≤ 20,000/mm3. Use of hydroxyurea to control blast count is permitted. * Patients must be status post allo-HCT (including: matched related, matched unrelated, haploidentical, mismatched unrelated; and cord blood HCT). * Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 * Adequate organ function, defined as: * Hepatic transaminase (both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 times the institutional upper limit of normal (ULN), * Total bilirubin level ≤1.5 times the ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤2.5 times the ULN), * Creatinine clearance of ≥50 ml/min * Adequate organ reserve including cardiovascular (ejection fraction within institutional normal limits), pulmonary (baseline pulmonary function test \[PFT\]: carbon monoxide diffusion capacity in the lung \[DLCO\] \> 50%, forced expiratory volume in 1 second \[FEV1\] \> 70%), renal, and hepatic functioning sufficient, in the judgment of the Investigator, to undergo therapy. * Normal thyroid function or stable thyroid tests on supplementation, except euthyroid sick syndrome. * Recovery from toxicities of clinical consequence attributed to previous chemotherapy to CTCAE v4.0 Grade ≤ 1 (i.e., certain toxicities such as alopecia will not be considered in this category). * Female patients of childbearing potential must test negative for pregnancy at enrollment and during the study. Sexually active women of child-bearing potential, unless surgically sterile, must be willing to use a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs) or vasectomized partner. Male patients with partners of childbearing potential must be either vasectomized or agree to use a condom in addition to having their partners use another method of contraception resulting in a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, or IUDs. Patients should not have sexual intercourse with females who are either pregnant or lactating without a condom. Contraception should be employed from the time of consent through 12 weeks after MGD006 administration. Patients should also abstain from sperm/egg donation during the course of the study. * Able to have corticosteroids weaned to ≤0.5mg/kg prednisone/day (or equivalent) * Able to have non-steroidal immunosuppression discontinued, including: * mycophenolate (MMF) * calcineurin inhibitors (tacrolimus, cyclosporine) \*\*calcineurin inhibitors must be able to be discontinued at least 14 days prior to enrolling on study. * JAK inhibitors (ruxolitinib) * MTOR inhibitors (sirolimus) * At least 18 years of age. * Ability to understand and willingness to sign an IRB approved written informed consent document Recipient
Exclusion criteria
* Active GVHD requiring systemic immunosuppression with more than 0.5 mg/day prednisone * Currently receiving any other investigational agents. * 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 (chemotherapy, radiotherapy, antibody therapy, molecular- targeted therapy, retinoid therapy, or investigational agent) within 5 half-lives of Cycle 1 Day 1 * At the time of study entry, steroids \>0.5mg/kg of prednisone or equivalent (except steroid inhaler, nasal spray or ophthalmic solution which are allowed). * Use of immunosuppressant medications (other than steroids as noted) in the 2 weeks prior to study drug administration (Cycle 1 Day 1). * Isolated extramedullary relapse (i.e., no evidence of bone marrow involvement). * Known central nervous system (CNS) leukemia. Patients with suspected CNS leukemia must be evaluated by lumbar puncture and be free of CNS disease prior to study entry. Previously treated CNS leukemia is allowed provided adequate treatment has been provided and the patient is free of CNS disease. * Any medical or psychiatric condition limiting full compliance or increasing the safety risk, at the discretion of the PI, such as: * active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection), * known human immunodeficiency virus infection, * known, active, or chronic hepatitis B or C infection (appropriately treated HBV/HCV infections with documented clearance of viral titer are allowed), * Grade 3 or 4 bleeding, * significant pulmonary compromise including chronic supplemental oxygen use, history of non-infectious pneumonitis (including radiation pneumonitis), pulmonary fibrosis, or severe chronic obstructive pulmonary disease (COPD), * uncontrolled (persistent) hypertension (systolic pressure \> 180 mm Hg or diastolic pressure \> 100 mm Hg * clinically significant arrhythmia, clinically significant baseline QTcF \>480 msec, * unstable angina, * recent myocardial infarction within 6 months prior to study drug administration (Cycle 1 Day 1), * clinically significant heart disease, such as, congestive heart failure, history of pericarditis, myocarditis, * history of stroke or transient ischemic event within 3 months prior to study drug administration (Cycle 1 Day 1), * untreated pulmonary embolism, or non-catheter-related deep-vein thrombosis in the 3 months prior to study drug administration (Cycle 1 Day 1), * pregnancy, or breast feeding, * major surgery or trauma within 4 weeks before enrollment. * Known hypersensitivity to murine, yeast, or recombinant proteins; polysorbate 80; recombinant human serum albumin; benzyl alcohol; or any excipient contained in the MGD006 drug formulation. * Dementia or altered mental status that would preclude sufficient understanding to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi | At the end of Cycle 1 (each cycle is 28 days) | * Complete remission without minimal residual disease (CRmrd): CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | At the end of Cycle 2 (each cycle is 28 days) | * Defined as partial remission or better * PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50% |
| Morphologic Leukemia-free State (MLFS) Rate | At the end of Cycle 2 (each cycle is 28 days) | \- MLFS: Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required |
| Partial Remission (PR) Rate | At the end of Cycle 2 (each cycle is 28 days) | \- PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50% |
| Stable Disease (SD) Rate | At the end of Cycle 2 (each cycle is 28 days) | \- SD: Absence of CR(mrd), CR, CRi, PR, MLFS; and criteria for PD not met |
| Progression-free Survival (PFS) Rate | Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days) | * PFS will be calculated as the time from the start of the first dose of study drug until the occurrence of disease progression or death from any cause, respectively * Progressive disease: Evidence for an increase in bone marrow blast percentage (\>50% over baseline), and/or increase of absolute blast counts in the blood (\>50% to \>25 × 10\^9/L) without differentiation syndrome, or new extramedullary disease |
| Efficacy as Measured by Number of Participants With CR and CRi | At the end of Cycle 2 (each cycle is 28 days) | * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\]) |
| Number of Participants With Adverse Events as Measured by CTCAE v5.0 | From start of treatment through 28 days following completion of treatment (median length of 59 days, full range 11-99 days). | — |
| Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Through the end of Cycle 2 (each cycle is 28 days) | * Grade 1:Symptoms are not life threatening and require symptomatic treatment only, e.g., fever, nausea, fatigue, headache, myalgias, malaise * Grade 2: Symptoms require and respond to moderate intervention; oxygen requirement \< 40% or hypotension responsive to fluids or low-dose of one vasopressor or grade 2 organ toxicity * Grade 3: Symptoms require and respond to aggressive intervention; oxygen requirement ≥ 40% or hypotension requiring high-dose vasopressors or multiple vasopressors or grade 3 organ toxicity (except transaminitis) or grade 4 transaminitis * Grade 4: Life-threatening symptoms; requirement for ventilator support or grade 4 organ toxicity (excluding transaminitis) * Grade 5 Death |
| Number of Participants With Neurotoxicity as Measured by 2019 ASTCT Consensus Guidelines | Through the end of Cycle 2 (each cycle is 28 days) | — |
| Number of Participants With Acute Graft Versus Host Disease (GvHD) as Measured by MAGIC Criteria | Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days) | — |
| Number of Participants With Chronic Graft Versus Host Disease (GvHD) as Measured by NIH Severity Score | Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days) | — |
| Overall Survival (OS) | Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days) | -OS will be calculated as the time from the start of the first dose of study drug until the occurrence of death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flotetuzumab * Will start on cycle 1 day 1 on the dose escalation ramp schedule of flotetuzumab as a continuous intravenous (IV) infusion. Patients will be initiated at 30 ng/kg/day and have their dose increased daily to a target goal of 500 ng/kg/day by day 7
* Patients will continue on flotetuzumab at 500 ng/kg/day for the remaining 21 days of the 28 day cycle.
* On cycle 1 day 28, patients will undergo bone marrow biopsy for assessment of disease status. Patients who have achieved a CR/CRi will proceed to a second cycle per protocol, while patients with a PR or SD or better may proceed to cycle 2 with permission of the investigator. Patients with available donor lymphocytes may receive DLI concurrently with flotetuzumab during Cycle 1 and/or Cycle 2. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Did not complete cycle 1 due to disease progression | 2 |
Baseline characteristics
| Characteristic | Flotetuzumab |
|---|---|
| Age, Continuous | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 8 / 11 |
Outcome results
Primary
Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi
* Complete remission without minimal residual disease (CRmrd): CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi | 0 Participants |
Secondary
Efficacy as Measured by Number of Participants With CR and CRi
* Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 and 2 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Efficacy as Measured by Number of Participants With CR and CRi | 0 Participants |
Secondary
Morphologic Leukemia-free State (MLFS) Rate
\- MLFS: Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment (or Cycle 1 Day 28 assessment for patients who only received Cycle 1 of treatment).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Morphologic Leukemia-free State (MLFS) Rate | 0 Participants |
Secondary
Number of Participants With Acute Graft Versus Host Disease (GvHD) as Measured by MAGIC Criteria
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Number of Participants With Acute Graft Versus Host Disease (GvHD) as Measured by MAGIC Criteria | 1 Participants |
Secondary
Number of Participants With Adverse Events as Measured by CTCAE v5.0
Time frame: From start of treatment through 28 days following completion of treatment (median length of 59 days, full range 11-99 days).
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dysuria | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hematuria | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hemoglobinuria | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 proteinuria | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 anemia | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 febrile neutropenia | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 sinus tachycardia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 adrenal insufficiency | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 anisocoria | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 conjunctivitis | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 scleral hemorrhage | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 blurred vision | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dry eye | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 melena | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 white tongue | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 abdominal distension | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 abdominal pain | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 abdominal pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 bloating | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 constipation | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 diarrhea | 7 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dry mouth | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 esophageal pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 gastroesophageal reflux disease | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hemorrhoids | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 lower gastrointestinal hemorrhage | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 mucositis oral | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 nausea | 5 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 stomach pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 vomiting | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 joint pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 chills | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 5 disease progression | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 edema face | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 edema face | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 edema limbs | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 facial pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 fatigue | 9 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 fever | 9 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 fever | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 generalized edema | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 injection site reaction | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 malaise | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 pain | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 GvHD of the gut | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 cytokine release syndrome | 8 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 cytokine release syndrome | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 enterococcus | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2staphylococcus aureus | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 bacteremia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 enterocolitis infectious | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 lung infection | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 sepsis | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 sinusitis | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 viremia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 deep tissue injury | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 fall | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 infusion related reaction | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 activated partial thromboplastin time prolonged | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 alanine aminotransferase increased | 7 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 alanine aminotransferase increased | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 alkaline phosphatase increased | 5 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 alkaline phosphatase increased | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 aspartate aminotransferase increased | 8 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 blood bilirubin increased | 8 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 creatinine increased | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 INR increased | 6 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 lymphocyte count decreased | 10 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 neutrophil count decreased | 7 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 platelet count decreased | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 weight gain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 white blood cell decreased | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 white blood cell decreased | 8 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 anorexia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 anorexia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dehydration | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypercalcemia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hyperglycemia | 6 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 hyperglycemia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hyperkalemia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 hyperkalemia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypermagnesemia | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypernatremia | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hyperphosphatemia | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypoalbuminemia | 6 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 hypoalbuminemia | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypocalcemia | 7 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 hypocalcemia | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypoglycemia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypokalemia | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hyponatremia | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypophosphatemia | 9 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 finger stiffness | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 groin pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 groin swelling | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 knee pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 shoulder pain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 arthralgia | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 arthralgia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 back pain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 back pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 bone pain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 bone pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 flank pain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 generalized muscle weakness | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 neck pain | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 neck pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 pain in extremity | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 expressive aphasia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dizziness | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 dizziness | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dysgeusia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dysphasia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 headache | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 peripheral sensory neuropathy | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 somnolence | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 syncope | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 tremor | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 incoherent | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 mental status slightly altered | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 agitation | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 agitation | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 anxiety | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 confusion | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 confusion | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hallucinations | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 insomnia | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 restlessness | 3 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 acute kidney disease | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dieresis | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 fractional excretion of sodium | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 urinary retention | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 sinus pressure | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 atelectasis | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 cough | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 dyspnea | 5 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 dyspnea | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 epistaxis | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypoxia | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 nasal congestion | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 productive cough | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 pulmonary edema | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 respiratory failure | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 sinus pain | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 sore throat | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 wheezing | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 oral lesion, left margin of tongue | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 acute GvHD | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 pain of skin | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 pruritus | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 rash maculo-papular | 2 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 skin ulceration | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 flushing | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hot flashes | 1 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 1-2 hypotension | 4 Participants |
| Flotetuzumab | Number of Participants With Adverse Events as Measured by CTCAE v5.0 | Grade 3-5 hypotension | 1 Participants |
Secondary
Number of Participants With Chronic Graft Versus Host Disease (GvHD) as Measured by NIH Severity Score
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Number of Participants With Chronic Graft Versus Host Disease (GvHD) as Measured by NIH Severity Score | 1 Participants |
Secondary
Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines
* Grade 1:Symptoms are not life threatening and require symptomatic treatment only, e.g., fever, nausea, fatigue, headache, myalgias, malaise * Grade 2: Symptoms require and respond to moderate intervention; oxygen requirement \< 40% or hypotension responsive to fluids or low-dose of one vasopressor or grade 2 organ toxicity * Grade 3: Symptoms require and respond to aggressive intervention; oxygen requirement ≥ 40% or hypotension requiring high-dose vasopressors or multiple vasopressors or grade 3 organ toxicity (except transaminitis) or grade 4 transaminitis * Grade 4: Life-threatening symptoms; requirement for ventilator support or grade 4 organ toxicity (excluding transaminitis) * Grade 5 Death
Time frame: Through the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Flotetuzumab | Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Grade 1 | 1 Participants |
| Flotetuzumab | Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Grade 2 | 7 Participants |
| Flotetuzumab | Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Grade 3 | 3 Participants |
| Flotetuzumab | Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Grade 4 | 0 Participants |
| Flotetuzumab | Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines | Grade 5 | 0 Participants |
Secondary
Number of Participants With Neurotoxicity as Measured by 2019 ASTCT Consensus Guidelines
Time frame: Through the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Number of Participants With Neurotoxicity as Measured by 2019 ASTCT Consensus Guidelines | 4 Participants |
Secondary
Overall Response Rate
* Defined as partial remission or better * PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment (or Cycle 1 Day 28 assessment for patients who only received Cycle 1 of treatment).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Overall Response Rate | 0 Participants |
Secondary
Overall Survival (OS)
-OS will be calculated as the time from the start of the first dose of study drug until the occurrence of death from any cause.
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Population: Protocol defined evaluability for participants is defined as having undergone any period of infusion of flotetuzumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Flotetuzumab | Overall Survival (OS) | 2.66 months |
Secondary
Partial Remission (PR) Rate
\- PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment (or Cycle 1 Day 28 assessment for patients who only received Cycle 1 of treatment).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Partial Remission (PR) Rate | 2 Participants |
Secondary
Progression-free Survival (PFS) Rate
* PFS will be calculated as the time from the start of the first dose of study drug until the occurrence of disease progression or death from any cause, respectively * Progressive disease: Evidence for an increase in bone marrow blast percentage (\>50% over baseline), and/or increase of absolute blast counts in the blood (\>50% to \>25 × 10\^9/L) without differentiation syndrome, or new extramedullary disease
Time frame: Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment (or Cycle 1 Day 28 assessment for patients who only received Cycle 1 of treatment).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Flotetuzumab | Progression-free Survival (PFS) Rate | 1.14 months |
Secondary
Stable Disease (SD) Rate
\- SD: Absence of CR(mrd), CR, CRi, PR, MLFS; and criteria for PD not met
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Population: Protocol defined evaluability for participants is defined as completing all Cycle 1 infusions of flotetuzumab (or discontinued treatment due to drug toxicity or disease progression) and undergone Cycle 2 Day 28 disease assessment (or Cycle 1 Day 28 assessment for patients who only received Cycle 1 of treatment).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flotetuzumab | Stable Disease (SD) Rate | 3 Participants |