Blastic Plasmacytoid Dendritic Cell NeoplasmPhase 1/2NCT03386513
Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN
A Phase 1/2 study testing IMGN632 in people with Blastic Plasmacytoid Dendritic Cell Neoplasm and Myeloproliferative Neoplasm, run by AbbVie at 29 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blastic Plasmacytoid Dendritic Cell Neoplasm, Myeloproliferative Neoplasm
- What is being tested?
- IMGN632
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 179 participants
- Where
- 29 sitesin 6 countries
- Study dates
- 2 Jan 2018to 30 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease Characteristics:
- 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-)
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
29 sites in 6 countries.
29 sites in 6 countries
United States16 sites
University of Maryland Medical Center
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
Novant Health Cancer Institute Hematology
Charlotte, North Carolina, 28204
Baylor Scott & White University Medical Center
Dallas, Texas, 75246
City of Hope Medical Center
Duarte, California, 91010
Duke Cancer Institute
Durham, North Carolina, 27710
Banner Health MD Anderson Cancer Center
Gilbert, Arizona, 85234
MD Anderson Cancer Center
Houston, Texas, 77030-7095
UCLA
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
Seattle, Washington, 98109
Stanford
Stanford, California, 94305
Moffitt Cancer Center
Tampa, Florida, 33612
Novant Health Cancer Institute Hematology - Forsyth
Winston-Salem, North Carolina, 27103
France5 sites
Recherche Clinique-Hématologie
Amiens
CHU de Besancon, Hopital Jean Minjoz
Besançon, 25030
Institut Paoli Calmettes (Marseille)
Marseille, 13009
Hôpital St Antoine
Paris
CHU Bordeaux Hôpital Haut-Lévêque
Pessac, 33600
Italy4 sites
IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi
Bologna, 40138
Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Instituto Europeo di Oncologia
Milan, 20141
Azienda ospedaliera Santa Maria della Misericordia
Perugia, 06132
Germany2 sites
University Hospital of Cologne
Cologne, 50937
University Hospital of Leipzig
Leipzig, 04103
About this study
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
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.
Read the detailed description
IMGN632 is administered by IV on Day 1 of each cycle, with cycles repeating every 21 days.
- Being tested
- IMGN632
- Keywords
- Antibody Drug Conjugate, Other Hematologic Malignancies, Myeloproliferative Neoplasms, CD123, MDS, Relapsed, Refractory, Acute Lymphocytic Leukaemia, Blastic Plasmacytoid Dendritic Cell Neoplasm, Acute Myeloid Leukemia
- Medical subject headings
- Blastic Plasmacytoid Dendritic Cell Neoplasm, Myeloproliferative Disorders, Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMGN632Drug
CD123-targeted ADC
| Study group | Role | What they receive |
|---|---|---|
| Escalation and Expansion | Experimental | 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. Receives: Drug: IMGN632 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Complete Remission/Response (CCR) Rate As Assessed by Investigator in Frontline De Novo Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Participants
CCR rate was defined as percentage of participants with complete remission/response (CR) and clinical complete remission (CRc). CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/microliter [μL]) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on computed tomography (CT); and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
Secondary outcomes (23)
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. This included an exacerbation of a pre-existing condition. SAEs included death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as any new AEs that begin or any pre-existing conditions that worsen in severity from the first dose of study drug through 30 days after the last dose or prior to the subsequent therapy, whichever occurs first.
Measured: Up to approximately 81 months
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was defined as all treatment-emergent adverse events (TEAEs) or abnormal laboratory values that met the protocol-defined DLT criteria, including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Up to approximately 81 months
Maximum Plasma Concentration (Cmax) of IMGN632 (Antibody Drug Conjugate [ADC]) and Total Antibody
Measured: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Cmax of FGN849
Measured: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IMGN632 (ADC) and Total Antibody
Measured: Cycle 1 and Cycle 3 (each cycle length = 21 days)
AUC0-last of FGN849
Measured: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Number of Participants With Anti-drug Antibodies (ADAs) at Any Post-baseline Visit
Measured: Up to approximately 81 months
Dose Escalation Phase: Overall Response Rate (ORR), As Assessed by Investigator in Participants With AML
ORR was defined as percentage of participants with CR without minimal residual disease (CRMRD-), CR, CR with partial hematologic recovery (CRh), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), or partial response (PR). CRMRD-: CR with negativity for a genetic marker. CR: Morphologic CR <5% blasts; Absolute neutrophil count (ANC) >1000/μL; Platelets ≥100,000/μL; Participant independent of transfusions; No residual evidence of active extramedullary disease; MRD+ or unknown. CRh: Met requirements for CR except ANC >500/μL and platelets >50,000/μL. CRi: Met requirements for CR except either ANC <1000/μL or platelets <100,000/μL. MLFS: Bone marrow <5% blasts in an aspirate with spicules; No blasts with Auer rods or persistence of extramedullary disease; Marrow not "aplastic"; ≥200 cells should be enumerated or cellularity should be ≥10%. PR: Decrease of ≥50% in percentage of blasts to 5% to 25% in bone marrow aspirate (BMA) and normalization of blood counts.
Measured: Up to approximately 81 months
Dose Escalation Phase: CR+CRh Rate, As Assessed by Investigator in Participants With AML
CR+CRh rate was defined as percentage of participants with CR, and CRh. CR: Morphologic CR <5% blasts; Absolute neutrophil count (ANC) >1000/μL; Platelets ≥100,000/μL; Participant independent of transfusions; No residual evidence of active extramedullary disease; MRD+ or unknown. CRh: Met requirements for CR except ANC >500/μL and platelets >50,000/μL.
Measured: Up to approximately 81 months
Dose Escalation Phase: CR+CRh+CRi Rate, As Assessed by Investigator in Participants With AML
CR+CRh+CRi rate was defined as percentage of participants with CR, CRh, or CRi. CR: Morphologic CR <5% blasts; Absolute neutrophil count (ANC) >1000/μL; Platelets ≥100,000/μL; Participant independent of transfusions; No residual evidence of active extramedullary disease; MRD+ or unknown. CRh: Met requirements for CR except ANC >500/μL and platelets >50,000/μL. CRi: Met requirements for CR except either ANC <1000/μL or platelets <100,000/μL.
Measured: Up to approximately 81 months
CCR Rate As Assessed by Investigator in Participants With Relapsed/Refractory (R/R) BPDCN
CCR rate was defined as percentage of participants with CR and CRc. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
Duration of CCR (DOCR) As Assessed by Investigator in Frontline De Novo BPDCN Participants With CR or CRc
DOCR was defined from the first response (CR or CRc) to the time of relapse or death from any cause, whichever came first. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. Median and 95% CI were calculated by Kaplan-Meier estimation.
Measured: Up to approximately 81 months
DOCR As Assessed by Investigator in R/R BPDCN Participants With CR or CRc
DOCR was defined from the first response (CR or CRc) to the time of relapse or death from any cause, whichever comes first. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
DOCR As Assessed by Investigator in Total Frontline BPDCN Participants With CR or CRc
DOCR was defined from the first response (CR or CRc) to the time of relapse or death from any cause, whichever comes first. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
Number of Participants With TEAEs in Participants Who Received IMGN632 As a Single Agent at the RP2D Level (0.045 mg/kg)
An AE was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. This included an exacerbation of a pre-existing condition. TEAEs were defined as any new AEs that began or any pre-existing conditions that worsen in severity from the first dose of study drug through 30 days after the last dose or prior to the subsequent therapy, whichever occurs first.. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Up to approximately 81 months
Rate of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants
Rate of CR+CRc+CRh: percentage of participants with CR, CRc, and CRh. CR: normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥1000/μL) and platelet count (≥100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc: normalization of blast percentage (≤5%); normalization of neutrophil count (≥1000/μL) and platelet count (≥100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRh: normalization of neutrophil count (≥ 500/μL) and platelet count (≥ 50,000/μL); other criteria same as defined for CRc.
Measured: Up to approximately 81 months
Duration of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants
Duration of CR+CRc+CRh was defined as time from first response to time of relapse or death from any cause, whichever came first. CR: normalization of blast percentage (≤5%); normalization of neutrophil count (≥1000/μL) and platelet count (≥100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc: normalization of blast percentage (≤5%); normalization of neutrophil count (≥1000/μL) and platelet count (≥100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRh: normalization of neutrophil count (≥ 500/μL) and platelet count (≥ 50,000/μL); other criteria same as defined for CRc.
Measured: Up to approximately 81 months
ORR As Assessed by Investigator in Total R/R BPDCN Participants
ORR: percentage of participants with CR, CRc, CRh, CRi, and PR. CR, CRc, and CRh as defined in Outcome Measure 20 above. CRi: normalization of blast percentage (≤5%); normalization of neutrophil count (≥1000/μL) or platelet count (≥100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. PR: Decreased by > 50% in blast percentage to 5%-25%; 50% to <100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; ≥50% decrease in the sum of the product of the diameters (SPD) of up to 6 largest dominant masses, no increase in size of other nodes; ≥ 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter), no increase in size of liver of spleen.
Measured: Up to approximately 81 months
Duration of Overall Response As Assessed by Investigator in Total R/R BPDCN Participants
Duration of overall response (CR, CRc, CRh, CRi, and PR) was defined as time from first response to time of relapse or death from any cause, whichever came first. CR, CRc, and CRh, CRi, and PR as defined in Outcome Measure 21 above.
Measured: Up to approximately 81 months
Overall Survival in Total R/R BPDCN Participants
Overall survival was defined as date of first dose until death from any cause.
Measured: Up to approximately 81 months
CCR Rate As Assessed by Investigator in All Frontline BPDCN Participants With Post-Treatment Consolidative Stem Cell Transplant (SCT)
CCR rate was defined as percentage of participants with CR and CRc. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
CCR Rate As Assessed by Investigator in All R/R BPDCN Participants With Post-Treatment Consolidative SCT
CCR rate was defined as percentage of participants with CR and CRc. CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Measured: Up to approximately 81 months
Percentage of Participants With Post-baseline Transfusion Independence in BPDCN Participants
Post-baseline transfusion independence (red blood cell [RBC] and platelet transfusion independence) was defined as any 56-day period after Cycle 1 Day 1 in which the participant did not receive either a RBC or platelet transfusion.
Measured: Up to approximately 81 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2017
- Study start2 Jan 2018
- Primary completion2 Oct 2024
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Blastic Plasmacytoid Dendritic Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03386513
- Sponsor's protocol ID
- IMGN632-0801
- Other IDs
- 2024-514195-40-00
- Status last verified
- Aug 2026
- First submitted
- 21 Dec 2017
- Last updated
- 4 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pemmaraju N, Marconi G, Montesinos P, Lane AA, Mazzarella L, Sallman DA, Ulrickson ML, Schiller GJ, Erba HP, Wang ES, Walter RB, Deconinck E, Aribi A, Legrand O, Lebon D, Maisano V, Martinelli G, DeAngelo DJ, Derenzini E, Du Y, Lakshmikanthan S, Potluri J, Kantarjian HM, Daver NG. Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm. J Clin Oncol. 2026 Apr;44(10):861-873. doi: 10.1200/JCO-25-02083. Epub 2026 Feb 11.
PubMed 41671533Daver 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.
PubMed 38423051
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03386513
- Acronym / sponsor ID
- IMGN632-0801
- Keywords
- Antibody Drug Conjugate, Other Hematologic Malignancies, Myeloproliferative Neoplasms, CD123, MDS, Relapsed, Refractory, Acute Lymphocytic Leukaemia, Blastic Plasmacytoid Dendritic Cell Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 179 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 2 Jan 2018 (actual)
- Primary completion
- 2 Oct 2024 (actual)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 29 Dec 2017 (actual)
- Results
- Posted 4 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Escalation and Expansion | Experimental | Drug: IMGN632Escalation: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Disease Characteristics:
- Expansion inclusion:
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMGN632CD123-targeted ADC | Drug | Escalation and Expansion |
Primary outcome
Composite Complete Remission/Response (CCR) Rate As Assessed by Investigator in Frontline De Novo Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Participants
Time frame: Up to approximately 81 months
CCR rate was defined as percentage of participants with complete remission/response (CR) and clinical complete remission (CRc). CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/microliter [μL]) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on computed tomography (CT); and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
23 secondary outcomes
Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 81 months
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Up to approximately 81 months
Maximum Plasma Concentration (Cmax) of IMGN632 (Antibody Drug Conjugate [ADC]) and Total Antibody
Time frame: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Cmax of FGN849
Time frame: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IMGN632 (ADC) and Total Antibody
Time frame: Cycle 1 and Cycle 3 (each cycle length = 21 days)
AUC0-last of FGN849
Time frame: Cycle 1 and Cycle 3 (each cycle length = 21 days)
Number of Participants With Anti-drug Antibodies (ADAs) at Any Post-baseline Visit
Time frame: Up to approximately 81 months
Dose Escalation Phase: Overall Response Rate (ORR), As Assessed by Investigator in Participants With AML
Time frame: Up to approximately 81 months
Dose Escalation Phase: CR+CRh Rate, As Assessed by Investigator in Participants With AML
Time frame: Up to approximately 81 months
Dose Escalation Phase: CR+CRh+CRi Rate, As Assessed by Investigator in Participants With AML
Time frame: Up to approximately 81 months
CCR Rate As Assessed by Investigator in Participants With Relapsed/Refractory (R/R) BPDCN
Time frame: Up to approximately 81 months
Duration of CCR (DOCR) As Assessed by Investigator in Frontline De Novo BPDCN Participants With CR or CRc
Time frame: Up to approximately 81 months
DOCR As Assessed by Investigator in R/R BPDCN Participants With CR or CRc
Time frame: Up to approximately 81 months
DOCR As Assessed by Investigator in Total Frontline BPDCN Participants With CR or CRc
Time frame: Up to approximately 81 months
Number of Participants With TEAEs in Participants Who Received IMGN632 As a Single Agent at the RP2D Level (0.045 mg/kg)
Time frame: Up to approximately 81 months
Rate of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants
Time frame: Up to approximately 81 months
Duration of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants
Time frame: Up to approximately 81 months
ORR As Assessed by Investigator in Total R/R BPDCN Participants
Time frame: Up to approximately 81 months
Duration of Overall Response As Assessed by Investigator in Total R/R BPDCN Participants
Time frame: Up to approximately 81 months
Overall Survival in Total R/R BPDCN Participants
Time frame: Up to approximately 81 months
CCR Rate As Assessed by Investigator in All Frontline BPDCN Participants With Post-Treatment Consolidative Stem Cell Transplant (SCT)
Time frame: Up to approximately 81 months
CCR Rate As Assessed by Investigator in All R/R BPDCN Participants With Post-Treatment Consolidative SCT
Time frame: Up to approximately 81 months
Percentage of Participants With Post-baseline Transfusion Independence in BPDCN Participants
Time frame: Up to approximately 81 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41671533Pemmaraju N, Marconi G, Montesinos P, Lane AA, Mazzarella L, Sallman DA, Ulrickson ML, Schiller GJ, Erba HP, Wang ES, Walter RB, Deconinck E, Aribi A, Legrand O, Lebon D, Maisano V, Martinelli G, DeAngelo DJ, Derenzini E, Du Y, Lakshmikanthan S, Potluri J, Kantarjian HM, Daver NG. Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm. J Clin Oncol. 2026 Apr;44(10):861-873. doi: 10.1200/JCO-25-02083. Epub 2026 Feb 11.
- Derived from this study: PubMed 38423051Daver 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
29 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IMGN632 in people with Blastic Plasmacytoid Dendritic Cell Neoplasm and Myeloproliferative Neoplasm, run by AbbVie at 29 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, France, Italy, Germany, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Complete Remission/Response (CCR) Rate As Assessed by Investigator in Frontline De Novo Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Participants (time frame: Up to approximately 81 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03386513, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.