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 - IMGN632-0801

Studio Clinico

Patologia: Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Linee di trattamento: Prima/N linee

Criteri di inclusione: 

- Disease Characteristics:
a. Confirmation of CD123 positivity by flow cytometry or IHC. Patients who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.
- Expansion inclusion:
    - Cohort 1 - Patients with relapsed or refractory BPDCN with 1-3 prior lines of therapy
    - Cohort 2 - Patients will have relapsed AML.
    - Cohort 3 - Patients will have relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+, and Ph-).
    - Cohort 4 - Patients will have relapsed or refractory 'other' hematologic malignancies not included in the cohorts above (eg, high-risk/very high-risk MDS, MPN, CMML, BP- CML). Other CD123+ malignancies may be considered upon discussion with the Sponsor.
    - Cohort 5 - Patients will have relapsed or refractory (to non-intense therapies) AML.
    - Cohort 6 - Patients with frontline BPDCN who have not received prior systemic therapy.
Note: Patients in Cohort 6 may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible patients must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy.

Criteri di esclusione: 

- Patients who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5.
- Frontline BPDCN patients 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 patients 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.
- Patients with a history of veno-occlusive disease of the liver.
- Patients 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 patients with prior local therapy (eg, radiotherapy), patients must not have received treatment within 14 days prior to drug administration on this study. 2. Relapsed or refractory BPDCN patients 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. Patients must have recovered to baseline from all acute toxicity from this prior therapy.
Note: the exception that patients who have received a checkpoint inhibitor must not have received that therapy within 28 days prior to drug administration on this study.

Trattamento sperimentale: 

IMGN632

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

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

Obiettivi secondari dello studio: 

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

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT03386513

Data di inserimento: 10.12.2021

Data di aggiornamento: 28.03.2023

Promotore

ImmunoGen, Inc.

Principal Investigator ITALIA

Istituto Romagnolo per la cura dei Tumori 'Dino Amadori' - IRST IRCCS, Meldola

Riferimento: Prof. Giovanni Martinelli

Telefono: 0543739100

Email: giovanni.martinelli@irst.emr.it

Localita: Meldola (FC)