Clinical Trials /

Study of IMGN632 in Patients With Relapse/Refractory AML, BPDCN, ALL, Other CD123+ Hem Malignancies

NCT03386513

Description:

This is an open-label, multi-center, Phase 1 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and preliminary anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of IMGN632 in Patients With Relapse/Refractory AML, BPDCN, ALL, Other CD123+ Hem Malignancies
  • Official Title: A Phase 1, Multi-center, Open-label Study of IMGN632 Administered Intravenously in Patients With Relapsed/Refractory CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: IMGN632-0801
  • NCT ID: NCT03386513

Conditions

  • Acute Lymphocytic Leukaemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Myeloproliferative Neoplasm
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
IMGN632Escalation and Expansion

Purpose

This is an open-label, multi-center, Phase 1 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and preliminary anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.

Detailed Description

      The study comprises a dose escalation phase followed by a dose expansion phase to further
      characterize the safety profile and confirm the MTD. IMGN632 will be administered IV on Day 1
      of each cycle, with cycles repeating every 21 days. Treatment will continue for up to 2
      cycles (6 weeks) in the absence of disease progression (PD), treatment intolerance, or
      withdrawal of consent.
    

Trial Arms

NameTypeDescriptionInterventions
Escalation and ExpansionExperimentalEscalation: IMGN632 will be administered by IV on Day 1 of each cycle, with cycles repeating every 21 days for patients with relapsed/refractory AML or BPDCN. Expansion: IMGN632 will be administered by IV on Day 1 of each cycle, with cycles repeating every 21 days, across four expansion cohorts, for patients with relapsed BPDCN, AML, ALL, and other CD123+ hematologic malignancies
  • IMGN632

Eligibility Criteria

        Inclusion Criteria:

        - Disease Characteristics and allowable prior therapy:

          -  Patients in dose escalation and all expansion cohorts except first relapse AML may
             have received up to three prior lines of therapy.

          -  Dose Escalation - Relapsed or refractory AML (excluding acute promyelocytic leukemia)
             or BPDCN, based on World Health Organization Classification. All patients enrolled on
             this study will have CD123+ disease.

          -  Dose Expansion Cohort #1 - Patients will have relapse of CD123+ BPDCN. Patients with
             prior CD123-targeting agents will be allowed as long as the blasts still have
             detectable CD123 expression.

          -  Dose Expansion Cohort #2 - Patients will have first relapse of CD123+ AML.

          -  Dose Expansion Cohort #3 - Patients will have relapse of CD123+ ALL.

          -  Dose Expansion Cohort #4 - Patients will have relapse of CD123+ "other" hematologic
             malignancies not included in the cohorts above (e.g., high-risk/very high-risk MDS,
             MPN, CMML, CML blast crisis). Other CD123+ malignancies may be considered upon
             discussion with the Medical Monitor.

        Exclusion Criteria:

          -  Patients who, in the judgment of their treating physician, have available standard of
             care therapies will be excluded

          -  AML patients with active central nervous system (CNS) disease will be excluded.

          -  Patients with a history of venous occlusive disease of the liver

          -  Patients with a history of Grade 3-4 capillary leak syndrome, or non-cardiac Grade
             edema are ineligible, e.g., related to SL-401 or other etiology

          -  Myocardial infarction within six months prior to enrollment or has New York Heart
             Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities prior to study entry

          -  Patients who have received any anti-cancer therapy including chemotherapy,
             immunotherapy, radiotherapy, hormonal, biologic, or any investigational agents within
             14 days or five half-lives, whichever is greater (with exception of hydroxyurea),
             prior to drug administration on this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) and recommended Ph2 dose (RP2D)
Time Frame:28 Days
Safety Issue:
Description:To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of IMGN632 when administered as a single agent

Secondary Outcome Measures

Measure:Treatment emergent adverse events
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Objective Response Rate (ORR) (complete response [CR= CR+CRp+CRi]+partial remission [PR])
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:PK parameters: maximum plasma concentration (Cmax) of IMGN632
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:PK parameters: area under the time-concentration curve (AUC) of IMGN632
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:PK parameters: terminal half-life (t½) of IMGN632
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Immunogenicity: Presence of Antibody-Drug Antibody (ADA)
Time Frame:Up to 12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

  • Antibody Drug Conjugate
  • Other Hematologic Malignancies
  • Myeloproliferative Neoplasms
  • CD123
  • MDS
  • Relapsed, Refractory
  • Acute Lymphocytic Leukaemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Acute Myeloid Leukemia

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