Open-label Study of IMGN779 in Adult Patients With Relapsed/Refractory CD33-positive Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is an open label, multicenter Phase 1 study to determine the MTD, dosing schedule and RP2D of IMGN779 when administered as mono-therapy to adult AML patients with CD33 -positive disease.

Detailed Description
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In the Dose Escalation Phase, patients will be assigned to one of three schedules. The MTD for all schedules will be determined from the assessment of Dose Limiting Toxicities (DLTs). The Dose Expansion Phase will consist of one cohort based on patients response to prior therapy according to the MTD selected.

Official Title
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A Phase 1, Multi-center, Open-label Study of IMGN779 Administered Intravenously in Adult Patients With Relapsed/Refractory CD33-positive Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: IMGN779


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dose Escalation: Patients with relapsed or refractory AML Dose Expansion: Patients with relapsed AML or patients who refuse, or are not suitable candidates for induction therapy Exclusion Criteria: Dose Escalation: Acute Promyelocytic Leukemia Any concurrent anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational agents (with the exception of hydroxyurea or leukapheresis for control of hyperleukocytosis) within 14 days or five half-lives of drugs, whichever is shorter, prior to Cycle 1 Day 1 AML patients with known, active leptomeningeal/central nervous system (CNS) involvement Prior treatment with IMGN779 Women who are pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Schedule A<br>IMGN779 administered on days 1 and 15 of a 28-day cycle | Drug: IMGN779<br> <br> |
| Experimental: Dose Escalation Schedule B<br>IMGN779 administered on days 1, 8, 15 and 22 of a 28-day cycle | Drug: IMGN779<br> <br> |
| Experimental: Dose Escalation Schedule C<br>IMGN779 administered on days 1 and 8 of a 21-day cycle | Drug: IMGN779<br> <br> |
| Experimental: Dose Expansion Cohort<br>Patients with Relapsed AML; IMGN779 administered at dose and schedule selected as the putative RP2D. | Drug: IMGN779<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of IMGN779 |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events |  | Up to 12 months | 
| Objective Response Rate (ORR) (complete response [CR= CR+CRp+CRi]+partial remission [PR]) |  | Up to 12 months | 
| PK parameters: maximum plasma concentration (Cmax) of IMGN779 |  | up to 12 months | 
| PK parameters: area under the time-concentration curve (AUC) of IMGN779 |  | Up to 12 months | 
| PK parameters: terminal half-life (t½) of IMGN779 |  | Up to 12 months | 
| Immunogenicity: Presence of Antibody-Drug Antibody (ADA) |  | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, AML, IMGN779, ImmunoGen, Phase 1, Relapsed, Refractory, CD33, Dose Escalation, Dose Expansion