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

Myeloproliferative Neoplasm Clinical Trial

Official title:

A Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients With CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03386513
• Other study ID #: IMGN632-0801
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2, 2018
• Est. completion date: December 2025

Study information

• Verified date: August 2023
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 179
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms

Intervention

Drug:
• IMGN632
CD123-targeted ADC

Locations

Country	Name	City	State
France	Recherche Clinique-Hématologie	Amiens
France	CHU de Besancon, Hopital Jean Minjoz	Besançon
France	Institut Paoli Calmettes (Marseille)	Marseille
France	Hôpital St Antoine	Paris
France	CHU Bordeaux Hôpital Haut-Lévêque	Pessac
Germany	University Hospital of Cologne	Cologne
Germany	University Hospital of Leipzig	Leipzig
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi	Bologna
Italy	Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Instituto Europeo di Oncologia	Milano
Italy	Azienda ospedaliera Santa Maria della Misericordia	Perugia
Spain	Hospital Universitari I Politècnic La Fe	Valencia
United Kingdom	Churchill Hospital - Oxford	Oxford
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Novant Health Cancer Institute Hematology	Charlotte	North Carolina
United States	Baylor Scott & White University Medical Center	Dallas	Texas
United States	City of Hope Medical Center	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	Banner Health MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	UCLA	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	Novant Health Cancer Institute Hematology - Forsyth	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the rate of composite CR in BPDCN patients	CR+clinical CR [CRc]	21-day cycle
Secondary	To assess the duration of CR (DOCR) for patients with CR or CRc		Up to 24 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03		Up to 24 months
Secondary	To assess the rate of CR+CRc+CRh		Up to 24 months
Secondary	To assess the duration of CR+CRc+CRh		Up to 24 months
Secondary	To assess ORR: CR+CRc+CRh+CRi+PR		Up to 24 months
Secondary	To assess the duration of overall response		Up to 24 months
Secondary	To assess OS		Up to 24 months
Secondary	To assess the percent of BPDCN patients able to bridge to stem cell transplant in the frontline and relapsed/refractory populations separately		Up to 24 months
Secondary	To characterize the PK of IMGN632, total antibody, and FGN849 (the active catabolite)		Up to 24 months
Secondary	To evaluate the potential immunogenicity of IMGN632	ADA	Up to 24 months
Secondary	To assess transfusion independence	Conversion rate to independence of red blood cell (RBC) and platelet transfusion relative to baseline	Up to 24 months