PIVEKIMAB SUNIRINE for Acute myeloid leukemia | Other hematologic malignancies

Inclusion criteria

• {"criterion_text":"-Disease Characteristics: a. Confirmation of CD123 positivity by flow cytometry or immunohistochemistry. Patients who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression b. Dose Escalation – Relapsed or refractory AML (excluding acute promyelocytic leukemia) or BPDCN, based on World Health Organization Classification. c. Dose Expansion - Cohort 1 - Patients with relapsed or refractory BPDCN - Cohort 2 – Patients will have relapsed AML (closed to enrollment). - Cohort 3 – Patients will have relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+ and Ph-) (closed to enrollment). - Cohort 4 – Patients will have relapsed or refractory other hematologic malignancies not included in the cohorts above (e.g., high-risk/very high-risk MDS, MPN, CMML, BP-CML). Other CD123+ malignancies may be considered upon discussion with the Sponsor. Note: BP-CML is defined as ≥ 30% blasts in blood, marrow, or both and the demonstration of extramedullary infiltrates of leukemic cells. - Cohort 5 – Patients will have relapsed or refractory (to nonintense therapies) AML (closed to enrollment). - Cohort 6 – Patients with frontline de novo BPDCN at screening who have not received prior systemic therapy and patients with frontline BPDCN who have a PCHM and 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. Patients identified as having concomitant malignancy while on trial will continue to be identified as de novo BPDCN patients."}
• {"criterion_text":"-ECOG performance status ≤ 1. If nonambulatory due to a chronic disability, must be Karnofsky performance status > 70."}
• {"criterion_text":"-Previous treatment related toxicities must be resolved to Grade 1 (excluding alopecia)."}
• {"criterion_text":"-Liver enzymes (aspartate aminotransferase and alanine aminotransferase) ≤ 2.5 × the upper limit of normal (ULN). Exceptions may be made for patients with elevated liver transaminases secondary to the underlying study disease."}
• {"criterion_text":"-Total bilirubin ≤ 1.5 × ULN; patients with Gilbert syndrome must have total bilirubin < 3.0 × ULN with direct bilirubin < 1.0 × ULN at the time of enrollment."}
• {"criterion_text":"-Estimated glomerular filtration rate of > 30 mL/min/1.73m2 or creatinine clearance of > 30 mL/min."}
• {"criterion_text":"-Left ventricular ejection fraction ≥ 45%."}
• {"criterion_text":"-Patients must not be incarcerated and must be freely willing and able to provide informed consent. Examples of patients unable to freely provide informed consent may include some adults under legal protection measure (eg, under guardianship/curatorship) or unable to express their consent and select adults under psychiatric care. Investigator’s discretion should be applied."}
• {"criterion_text":"-Patients with a prior autologous or allogeneic bone marrow transplant are eligible for Cohorts 1 to 5. Patients with an allogeneic transplant must meet the following conditions: the transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 acute graft versus host disease (GvHD), or extensive chronic GvHD of any severity, and must be off all immunosuppression for at least 2 weeks before first dose of IMGN632."}
• {"criterion_text":"-Patients or their legally authorized representative must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), before performance of any study-related procedure not part of normal medical care."}
• {"criterion_text":"-Women of childbearing potential WCBP patients/partners, defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months) must agree to use acceptable contraceptive methods while on study drug and for at least 7 months after the last dose of study drug."}
• {"criterion_text":"-WCBP must have a negative pregnancy test before the first dose of study drug."}
• {"criterion_text":"-Male patients/partners who are able to father children must agree to use an effective method of contraception (eg, condoms), even if they have had a successful vasectomy, throughout the study and for at least 4 months after the last dose of IMGN632."}
• {"criterion_text":"-Patients with prior malignancy are eligible. Patient with a PCHM are eligible as long as no current therapy is required for the second malignancy (eg, MDS, CMML). Patients with a nonhematologic prior malignancy must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy for prior malignancy at least 6 months prior to enrollment and all treatment-related toxicities must have resolved to Grade 1 or less. Note: Patients with prostate cancer or breast cancer on adjuvant hormonal therapy are eligible. Note: Patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible"}
• {"criterion_text":"-Patients in the BPDCN Expansion Phase Cohort 1 may have received up to 3 prior lines of systemic therapy (regardless of tagraxofusp-erzs exposure)."}
• {"criterion_text":"-Age ≥ 18 years of age."}

Exclusion criteria

• {"criterion_text":"-Patients who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through 5."}
• {"criterion_text":"-Serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously compromise safety assessment or compliance with the protocol, in the judgment of the Investigator."}
• {"criterion_text":"-Patients who are pregnant or breast-feeding."}
• {"criterion_text":"-Patients who have a history of allergy to IMGN632 or any of its excipients."}
• {"criterion_text":"-Patients who received a live vaccine four weeks or fewer prior to enrollment"}
• {"criterion_text":"-Frontline BPDCN patients with CNS disease will be excluded. A lumbar puncture must be performed during the 28-day Screening period, before 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 before first dose. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is encouraged (see Section 5.2.4.1)."}
• {"criterion_text":"-Patients with a history of veno-occlusive disease of the liver."}
• {"criterion_text":"-Patients with a history of Grade 4 capillary leak syndrome, or noncardiac Grade 4 edema are ineligible, e.g., related to tagraxofusperzs or other etiology."}
• {"criterion_text":"-Corrected QT interval (QT interval corrected using Fridericia's) > 480 msec."}
• {"criterion_text":"-Myocardial infarction within 6 months before enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry."}
• {"criterion_text":"-Interval from prior cancer therapy: a. For frontline BPDCN patients with prior local therapy (eg, radiotherapy), patients must not have received treatment within 14 days before drug administration on this study. b. Relapsed or refractory BPDCN patients must not have received any anticancer 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: Patients who have received a checkpoint inhibitor must not have received that therapy within 28 days before drug administration on this study."}
• {"criterion_text":"-Clinically relevant active infection including known active hepatitis B or C, human immunodeficiency virus infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the Investigator, would make a patient inappropriate for enrollment into this study (testing not required)."}
• {"criterion_text":"-Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment."}

Primary endpoints

• {"endpoint_text":"-Escalation Phase: MTD and RP2D","definition_or_measurement_approach":""}
• {"endpoint_text":"-BPDCN: CR+clinical CR [CRc]","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"-Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and DLTs","definition_or_measurement_approach":"Collection and reporting of TEAEs, SAEs and dose-limiting toxicities as safety outcome measures during treatment (as described in protocol safety sections)."}
• {"endpoint_text":"-PK parameters, including but not limited to observed maximum concentration (Cmax) and area under the concentration versus time curve (AUC)","definition_or_measurement_approach":"Pharmacokinetic sampling to determine observed Cmax and AUC and other PK parameters for IMGN632, total antibody, and FGN849 (active catabolite)."}
• {"endpoint_text":"-To evaluate the potential immunogenecity of IMGN632 - ADA","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) to evaluate immunogenicity."}
• {"endpoint_text":"-Overall response rate (OOR) (CR without minimal residual disease [CRMRD- ] + CR + complete remission with partial hematologic recovery [CRh] + complete remission with incomplete recovery [CRi] + morphologic leukemia-free state [MLFS] + partial response [PR]), complete remission rate (CRMRD-, CR, CRh), composite complete remission (CCR) rate (CRMRD-, CR, CRh, CRi), and time to event outcomes (duration of overall response [DOR], event-free survival, relapse-free survival, OS).","definition_or_measurement_approach":"Response assessed using hematologic response categories (CRMRD-, CR, CRh, CRi, MLFS, PR); time-to-event outcomes measured as DOR, event-free survival, relapse-free survival and overall survival."}
• {"endpoint_text":"-BPDCN Expansion Phase (Cohorts 1 and 6): CR+CRc","definition_or_measurement_approach":"Assessment of complete remission and clinical complete remission rates in BPDCN expansion cohorts."}
• {"endpoint_text":"-BPDCN Expansion Phase (Cohorts 1 and 6): ADA","definition_or_measurement_approach":"Assessment of anti-drug antibodies in BPDCN expansion cohorts."}
• {"endpoint_text":"-BPDCN Expansion Phase (Cohorts 1 and 6): Conversion rate to independence of red blood cell and platelet transfusion relative to baseline","definition_or_measurement_approach":"Measure change from baseline in transfusion dependence (red blood cell and platelet transfusions) to evaluate conversion to transfusion independence."}

France

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

05-07-2024

Processing Time Days

49

Number Of Sites

2

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

17-05-2024

Latest Decision Or Authorization Date

08-07-2024

Processing Time Days

52

Number Of Sites

1

Number Of Participants

26

Primary sponsor

Full Name

AbbVie Deutschland GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

QPS LLC

Responsibilities

code:4

Name

Primevigilance USA Inc.

Responsibilities

code:8

Name

Precision For Medicine (UK) Limited

Responsibilities

codes:1,12,2,5,6,7

Name

PPD Global Central Labs

Responsibilities

code:4

Third parties

• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Roswell Park Comprehensive Cancer Center","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Hematologics Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Precision For Medicine (UK) Limited","duties_or_roles":"codes:1,12,2,5,6,7","organisation_type":"Pharmaceutical company"}