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

Phase 1

Active, not recruiting

Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm
Myeloproliferative Neoplasm

Interventions: Drug: IMGN632

Registration Number: NCT03386513

Lead Sponsor: AbbVie

Brief 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.

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

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 179

Inclusion Criteria

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.
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

Participants who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
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.
Participants with a history of veno-occlusive disease (sinusoidal obstruction syndrome) of the liver.
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.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Escalation and Expansion	IMGN632	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.

Primary Outcome Measures

Name	Time	Method
To assess the rate of composite CR in BPDCN patients	21-day cycle	CR+clinical CR \[CRc\]

Secondary Outcome Measures

Name	Time	Method
To assess ORR: CR+CRc+CRh+CRi+PR	Up to 24 months
To assess the duration of overall response	Up to 24 months
To assess the duration of CR+CRc+CRh	Up to 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	Up to 24 months
To assess the rate of CR+CRc+CRh	Up to 24 months
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
To assess the duration of CR (DOCR) for patients with CR or CRc	Up to 24 months
To assess OS	Up to 24 months
To characterize the PK of IMGN632, total antibody, and FGN849 (the active catabolite)	Up to 24 months
To evaluate the potential immunogenicity of IMGN632	Up to 24 months	ADA
To assess transfusion independence	Up to 24 months	Conversion rate to independence of red blood cell (RBC) and platelet transfusion relative to baseline

Trial Locations

Locations (28): University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
City of Hope Medical Center
🇺🇸
Duarte, California, United States
Novant Health Cancer Institute Hematology
🇺🇸
Charlotte, North Carolina, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
CHU Bordeaux Hôpital Haut-Lévêque
🇫🇷
Pessac, France
Hôpital St Antoine
🇫🇷
Paris, France
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, Italy
University Hospital of Cologne
🇩🇪
Cologne, Germany
Hospital Universitari I Politècnic La Fe
🇪🇸
Valencia, Spain
Baylor Scott & White University Medical Center
🇺🇸
Dallas, Texas, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Duke Cancer Institute
🇺🇸
Durham, North Carolina, United States
Novant Health Cancer Institute Hematology - Forsyth
🇺🇸
Winston-Salem, North Carolina, United States
University Hospital of Leipzig
🇩🇪
Leipzig, Germany
UCLA
🇺🇸
Los Angeles, California, United States
Stanford
🇺🇸
Stanford, California, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Recherche Clinique-Hématologie
🇫🇷
Amiens, France
CHU de Besancon, Hopital Jean Minjoz
🇫🇷
Besançon, France
Institut Paoli Calmettes (Marseille)
🇫🇷
Marseille, France
Churchill Hospital - Oxford
🇬🇧
Oxford, United Kingdom
Banner Health MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States