E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Acute Myeloid Leukemia or Intermediate-2/High Risk Myelodysplastic Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
- 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 6 months 3. Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): up to 2 induction (induction, reinduction) 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 < or = 2. 5. Life expectancy of at least 4 weeks. 6. Peripheral blast count < or = 20,000/mm3 at the time of registration (see related Exclusion Criterion 3). 7. Acceptable laboratory parameters and adequate organ reserve 8. Adult: Eighteen (18) years of age or older |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of each cycle of treatment; each cycle is 4 weeks long. |
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E.5.2 | Secondary end point(s) |
Efficacy Endpoint: To describe response rate, duration of response, event-free survival, overall survival and transplantation time. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
At the end of the study there will be 2 groups. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study will occur after the last patient has received the last dose of study drug and has been followed until disease progression, stem cell transplant, withdrawal of consent, or until death, whichever occurs first, and the data collection process is complete (time of study database lock). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |