Clinical trial NCT03386513: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm
Myeloproliferative Neoplasm
Keywords: Antibody Drug Conjugate
Other Hematologic Malignancies
Myeloproliferative Neoplasms
CD123
MDS
Relapsed, Refractory
Acute Lymphocytic Leukaemia
Blastic Plasmacytoid Dendritic Cell Neoplasm
Acute Myeloid Leukemia
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-12-29
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To assess the rate of composite CR in BPDCN patients
timeFrame: 21-day cycle
Secondary outcomes:
measure: To assess the duration of CR (DOCR) for patients with CR or CRc
timeFrame: Up to 24 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: Up to 24 months
measure: To assess the rate of CR+CRc+CRh
timeFrame: Up to 24 months
measure: To assess the duration of CR+CRc+CRh
timeFrame: Up to 24 months
measure: To assess ORR: CR+CRc+CRh+CRi+PR
timeFrame: Up to 24 months
measure: To assess the duration of overall response
timeFrame: Up to 24 months
measure: To assess OS
timeFrame: Up to 24 months
measure: To assess the percent of BPDCN patients able to bridge to stem cell transplant in the frontline and relapsed/refractory populations separately
timeFrame: Up to 24 months
measure: To characterize the PK of IMGN632, total antibody, and FGN849 (the active catabolite)
timeFrame: Up to 24 months
measure: To evaluate the potential immunogenicity of IMGN632
timeFrame: Up to 24 months
measure: To assess transfusion independence
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Stanford
country: United States
facility: Stanford
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute Hematology
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute Hematology - Forsyth
state: North Carolina
city: Dallas
country: United States
facility: Baylor Scott & White University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
state: Washington
city: Amiens
country: France
facility: Recherche Clinique-Hématologie
city: Besançon
country: France
facility: CHU de Besancon, Hopital Jean Minjoz
city: Marseille
country: France
facility: Institut Paoli Calmettes (Marseille)
city: Paris
country: France
facility: Hôpital St Antoine
city: Pessac
country: France
facility: CHU Bordeaux Hôpital Haut-Lévêque
city: Cologne
country: Germany
facility: University Hospital of Cologne
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi
city: Meldola
country: Italy
facility: Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Instituto Europeo di Oncologia
city: Perugia
country: Italy
facility: Azienda ospedaliera Santa Maria della Misericordia
city: Valencia
country: Spain
facility: Hospital Universitari I Politècnic La Fe
city: Oxford
country: United Kingdom
facility: Churchill Hospital - Oxford
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: