Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN

NCT ID: NCT03386513

Last Updated: 2024-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

179 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-02

Study Completion Date

2026-12-30

Brief Summary

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This is an open-label, multi-center, Phase 1/2 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.

Detailed Description

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IMGN632 is administered by IV on Day 1 of each cycle, with cycles repeating every 21 days.

Conditions

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Blastic Plasmacytoid Dendritic Cell Neoplasm Myeloproliferative Neoplasm

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Escalation and Expansion

Escalation: IMGN632 was administered by IV on 2 different schedules for participants with relapsed/refractory AML, ALL, or BPDCN.

Expansion: IMGN632 was administered by IV:

* Cohort 1: Relapsed or refractory BPDCN participants who have received 1-3 prior systemic therapies (incl. tagraxofusp-erzs and/or any other systemic therapy deemed appropriate for the treatment of BPDCN)
* Cohort 2: Relapsed AML
* Cohort 3: Relapsed or refractory ALL
* Cohort 4: Other relapsed or refractory hematologic malignancies
* Cohort 5: Relapsed or refractory AML at alternate dose or schedule
* Cohort 6: Pivotal cohort for frontline BPDCN participants who have not received prior systemic therapy and participants with frontline BPDCN who have prior or concomitant hematologic malignancy (PCHM) and have not received prior systemic therapy.

Group Type EXPERIMENTAL

IMGN632

Intervention Type DRUG

CD123-targeted ADC

Interventions

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IMGN632

CD123-targeted ADC

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Disease Characteristics:

a. Confirmation of CD123 positivity by flow cytometry or IHC. Participants who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.
2. Expansion inclusion:

* Cohort 1 - Participants with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) with 1-3 prior lines of therapy
* Cohort 2 - Participants with relapsed AML
* Cohort 3 - Participants with relapsed relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+ and Ph-)
* Cohort 4 - Participants with relapsed or refractory other hematologic malignancies not included in the cohorts above (eg, high risk/very high-risk MDS, MPN, CMML, BP-CML).
* Cohort 5 - Participants with relapsed relapsed or refractory (to nonintense therapies) CD123+ AML.
* Cohort 6 - Participants with frontline de novo BPDCN at screening who have not received prior systemic therapy and participants with frontline BPDCN who have PCHM and have not received prior systemic therapy.

Note: Participants in Cohort 6 may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible participants must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy.

Exclusion Criteria

1. Participants who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
2. Frontline BPDCN participants with central nervous system (CNS) disease will be excluded. A lumbar puncture must be performed during the 28-day screening period, prior to drug administration. Relapsed or refractory BPDCN participants with a known history of CNS disease must have been treated locally, have at least 1 lumbar puncture with no evidence of CNS disease, and must be clinically stable prior to first dose. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted with the approval of the Sponsor.
3. Participants with a history of veno-occlusive disease (sinusoidal obstruction syndrome) of the liver.
4. Participants with a history of Grade 4 capillary leak syndrome, or non-cardiac Grade 4 edema are ineligible, eg, related to tagraxofusp-erzs or other etiology.
5. Interval from prior cancer therapy: 1. For frontline BPDCN participants with prior local therapy (eg, radiotherapy), participants must not have received treatment within 14 days prior to drug administration on this study. 2. Relapsed or refractory BPDCN participants must not have received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agents within 14 days prior to drug administration on this study. Participants must have recovered to baseline from all acute toxicity from this prior therapy.

Note: the exception that participants who have received a checkpoint inhibitor must not have received that therapy within 28 days prior to drug administration on this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Banner Health MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

City of Hope Medical Center

Duarte, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

Stanford

Stanford, California, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Novant Health Cancer Institute Hematology

Charlotte, North Carolina, United States

Site Status

Duke Cancer Institute

Durham, North Carolina, United States

Site Status

Novant Health Cancer Institute Hematology - Forsyth

Winston-Salem, North Carolina, United States

Site Status

Baylor Scott & White University Medical Center

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Recherche Clinique-Hématologie

Amiens, , France

Site Status

CHU de Besancon, Hopital Jean Minjoz

Besançon, , France

Site Status

Institut Paoli Calmettes (Marseille)

Marseille, , France

Site Status

Hôpital St Antoine

Paris, , France

Site Status

CHU Bordeaux Hôpital Haut-Lévêque

Pessac, , France

Site Status

University Hospital of Cologne

Cologne, , Germany

Site Status

University Hospital of Leipzig

Leipzig, , Germany

Site Status

IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi

Bologna, , Italy

Site Status

Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Site Status

Instituto Europeo di Oncologia

Milan, , Italy

Site Status

Azienda ospedaliera Santa Maria della Misericordia

Perugia, , Italy

Site Status

Hospital Universitari I Politècnic La Fe

Valencia, , Spain

Site Status

Churchill Hospital - Oxford

Oxford, , United Kingdom

Site Status

Countries

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United States France Germany Italy Spain United Kingdom

References

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Daver NG, Montesinos P, DeAngelo DJ, Wang ES, Papadantonakis N, Todisco E, Sweet KL, Pemmaraju N, Lane AA, Torres-Minana L, Thompson JE, Konopleva MY, Sloss CM, Watkins K, Bedse G, Du Y, Malcolm KE, Zweidler-McKay PA, Kantarjian HM. Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. Lancet Oncol. 2024 Mar;25(3):388-399. doi: 10.1016/S1470-2045(23)00674-5.

Reference Type DERIVED
PMID: 38423051 (View on PubMed)

Other Identifiers

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2024-514195-40-00

Identifier Type: CTIS

Identifier Source: secondary_id

IMGN632-0801

Identifier Type: -

Identifier Source: org_study_id