A Phase 1/2, First-in-Human, Dose Escalation Study of MGD006, a CD123 x CD3 Dual Affinity Re-Targeting (DART) Bi-Specific Antibody-Based Molecule, in Patients with Relapsed or Refractory Acute Myeloid Leukemia or Intermediate-2/High Risk Myelodysplastic Syndrome
- Conditions
- bloodcancer10024324Acute Myeloid Leukemia
- Registration Number
- NL-OMON55771
- Lead Sponsor
- MacroGenics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Patients must have a confirmed diagnosis of primary or secondary AML (any
subtype except acute promyelocytic leukemia [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:
- An intensive induction attempt, per institution. Induction attempts include
high dose and/or standard-dose cytarabine +/- an anthracyclines/anthracenedione
+/- and anti-metabolite, with or without growth factor or targeted therapy
containing regimes.
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
- For adults who are age 75 years or older, who have comorbidities that
preclude use of intensive induction chemotherapy; PIF is defined as AML
refractory to one of the following less intensive regimes, 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 CR 1
duration < 6 months.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status less-than or
equal to 2.
5. Life expectancy of at least 4 weeks.
6. Peripheral blast count less-than or equal to 20,000/mm3 at the time of
first dose of study treatment (see related Exclusion Criterion 3).
7. Acceptable laboratory parameters and adequate organ reserve.
8. Adult: Eighteen (18) years of age or older.
1. Prior history of allogeneic stem cell transplantation
2. Prior treatment with an anti-CD123-directed agent.
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 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 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy based on CR/CRh rate:<br /><br>Proportion of patients achieving a best response of CR (morphologic CR,<br /><br>cytogenetic CR, molecular CR, or CRh per Interworking Group AML response<br /><br>criteria.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Efficacy Endpoint:<br /><br>response rate, duration of response, event-free survival, overall survival and<br /><br>transplantation rate</p><br>