A study to test IMGN632 in adults with CD123-positive Acute Myeloid Leukemia and other CD123 positive Hematologic cancers
- Conditions
- CD123 positive Acute Myeloid Leukemia and other CD123 positive hematologic malignanciesMedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003210-40-IT
- Lead Sponsor
- IMMUNOGEN, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 232
1. 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
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 OR patients with untreated BPDCN who are inappropriate for available therapies. BPDCN patients considered inappropriate for available therapies must be either >= 75 years of age OR 18 to 74 years of age if the patient has at least one comorbidity that the physician judges to be incompatible with intense and available therapies, eg, pulmonary, cardiac, hepatic, vascular comorbidities or is ineligible for available therapies, eg, hypoalbuminemia (serum albumin < 3.2 mg/dL) as an exclusion for tagraxofusp (ELZONRIS).
- 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 highrisk 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 non-intense therapies) CD123+ AML.
2. Prior therapies:
a. Patients in Dose Escalation and Dose Expansion Cohort #1, #3, and #4 may have received up to four prior lines of therapy.
b. Patients in Dose Expansion Cohort #2 with AML may have received up to two prior lines of therapy
c. Patients in Dose Expansion Cohort #5 with AML may have received up to three prior lines of therapy.
3. Age >= 18 years of age.
4. Eastern Cooperative Oncology Group performance status <= 1. If nonambulatory due to a chronic disability, must be Karnofsky performance status > 70.
5. Previous treatment related toxicities must have resolved to Grade 1 (excluding alopecia).
6. Liver enzymes (aspartate aminotransferase and alanine aminotransferase) <= 2.5 x the upper limit of normal (ULN). Exceptions may be made for patients with elevated liver transaminases secondary to the underlying study disease
7. Total bilirubin <= 1.5 x ULN within 14 days of enrollment.
8. Serum creatinine <= 1.5 × ULN within 14 days of enrollment.
9. Echocardiogram or multigated acquisition scan demonstrating an ejection fraction >= 45%.
10. Patients with a prior autologous and allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: the transplant must have been performed more than 120 days before the date of informed consent to this study, the patient must not have active >= Grade 2 acute graft versus host disease (GvHD), or either moderate or severe limited chronic GvHD, or extensive chronic GvHD of any severity; the patient must be off all immunosuppression for at least two weeks.
11. Voluntary written informed consent before performance of any study-related procedure not part of normal care.
[...]
For further details, please refer to protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subject
1.Patients who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded.
2.Patients with active central nervous system (CNS) disease will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of central nervous system involvement. All patients with a known history of CNS disease or brain metastasis must have been treated locally, have at least three consecutive lumbar punctures with no evidence of CNS disease, and must be clinically stable for at least four weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to active CNS disease (sequelae that are a consequence of prior CNS disease or the treatment are acceptable). Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted with the approval of the sponsor.
3.Patients with a history of venous occlusive disease of the liver.
4.Patients with a history of Grade 4 capillary leak syndrome, or non-cardiac Grade 4 edema are ineligible, e.g., related to SL-401 or other etiology.
5.Corrected QT interval (QTc Fridericia formula) > 480 msec.
6.Myocardial infarction within six months prior to 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 prior to study entry.
7.Patients who 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.
8.Clinically Relevant active infection including known active hepatitis B or C, human immunodeficiency virus infection, or cytomegalovirus or any other known concurrent infections disease that, in the judgment of the Investigator, would make a patient inappropriate for enrollment into this study (testing not required).
9.Patients who have undergone a major surgery within four weeks (or longer if not fully recovered) prior to study enrollment.
10.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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Escalation Phase: To determine the maximum tolerability of IMGN632 on<br>the selected dosing schedule(s)<br>BPDCN: To assess the response rate in BPDCN patients;Secondary Objective: 1. ALL Patients:<br>•To characterize the safety profile and tolerability of IMGN632 when given as a single agent across dose levels and schedules<br>•To characterize the PK of IMGN632, total antibody, and free payload (FGN849); IMGN632 metabolites may be evaluated<br>•To evaluate the potential immunogenicity of IMGN632<br>•To assess the preliminary anti-leukemia activity in AML and ALL patients (tumor-specific expansion cohorts) and BPDCN patients<br>2. BPDCN patients: to assess the durability of benefit in BPDCN patients;Primary end point(s): Escalation Phase:<br>MTD and RP2D<br><br>BPDCN:<br>Complete remission rate (CR/CRi/CRc/complete remission with partial hematologic recovery [CRh]);Timepoint(s) of evaluation of this end point: End of Study (MTD, RP2D)<br>
- Secondary Outcome Measures
Name Time Method