Relapsed or Refractory Acute Myeloid Leukemia or Intermediate-2/High Risk Myelodysplastic Syndrome MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
MacroGenics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a confirmed diagnosis of primary or secondary AML (any subtype except APL) according to World Health Organization (WHO) classification. 2. Patients with AML must meet one of the following criteria: a. Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, 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. One cycle of high dose cytarabine (HiDAC) containing regimen 2. One cycle of liposomal cytarabine and daunorubicin 3. Two 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, 1 or 2: 1. = 2 but = 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine 2. = 2 but = 4 cycles of gemtuzumab ozogamicin monotherapy b. Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration =65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: 1. Prior history of allogeneic stem cell transplantation 2. Prior treatment with an anti-CD123-directed agent, with the exclusion of patients with relapsed disease after MGD006 treatment. 3. Need for concurrent other cytoreductive chemotherapy 4. 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) 5. Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. 6. Antitumor therapy (chemotherapy, radiotherapy, antibody therapy, moleculartargeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives of Cycle 1 Day 1. 7. 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. 8. Use of immunosuppressant medications (other than steroids as noted) in the 2 weeks prior to study drug administration (Cycle 1 Day 1). 9. Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration (Cycle 1 Day 1). 10. Known central nervous system (CNS) leukemia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study going forward is to assess the antineoplastic activity of flotetuzumab in patients with PIF/ER AML, as determined by the proportion of patients who achieve complete remission (CR) or complete remission with partial hematologic recovery (CRh).;Secondary Objective: - To assess the response rate and the duration of response; - To characterize the pharmacokinetics (PK) and immunogenicity of MGD006; - To evaluate early mortality rates from any cause, overall survival (OS), and event-free survival (EFS); - To determine the rate of transition to stem cell transplant; - To determine safety and efficacy of tocilizumab in the treatment of IRR/CRS. ;Primary end point(s): Efficacy Endpoint Proportion of patients achieving a best response of CR (morpohologic CR [mCR], cytogenetic CR [CRc], molecular CR [CRm]), or CRh per Interworking Group AML response criteria.;Timepoint(s) of evaluation of this end point: At the end of each cycle of treatment; each cycle is 4 weeks long. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoint: To describe response rate, duration of response, event-free survival, overall survival and transplantation time.;Timepoint(s) of evaluation of this end point: Through end of treatment | — |
Countries
Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Project Manager
MacroGenics, Inc.
Outcome results
None listed