Purpose

This is an open-label, multi-center, Phase 1/2 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and preliminary anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease. The study is currently enrolling eligible AML, BPDCN and ALL patients.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Disease Characteristics:
  2. 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.
  3. Dose Escalation - Relapsed or refractory AML (excluding acute promyelocytic leukemia) or BPDCN, based on World Health Organization Classification
  4. Dose Expansion
  5. 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).
  6. Cohort #2 - Patients will have relapsed AML.
  7. Cohort #3 - Patients will have relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+ and Ph-)
  8. 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, CML blast crisis). Other CD123+ malignancies may be considered upon discussion with the Sponsor.
  9. Cohort #5 - Patients will have relapsed or refractory (to non-intense therapies) AML.
  10. Prior therapies:
  11. Patients in Dose Escalation and Dose Expansion Cohort #1, #3, and #4 may have received up to four prior lines of therapy.
  12. Patients in Dose Expansion Cohort #2 with AML may have received up to two prior lines of therapy.
  13. Patients in Dose Expansion Cohort #5 with AML may have received up to three prior lines of therapy.

Exclusion Criteria

  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.
  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 edema are ineligible, eg, related to SL-401 or other etiology
  5. 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
  6. Patients who have received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agents within 14 days or five half-lives, whichever is greater (with exception of hydroxyurea), prior to drug administration on this study.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Escalation and Expansion
Escalation: IMGN632 will be administered by IV on two different schedules for patients with relapsed/refractory AML or BPDCN: Schedule A: Day 1 of each cycle, with cycles repeating every 21 days Schedule B: Days 1, 4 and 8 of each cycle, with cycles repeating every 21 days Expansion: IMGN632 will be administered based on the recommended phase 2 dose (RP2D) and schedule as determined in the Escalation Phase, across five expansion cohorts, for patients with 1) relapsed, refractory OR selected untreated BPDCN; 2) relapsed AML; 3) relapsed or refractory ALL; 4) other relapsed or refractory CD123+ hematologic malignancies; 5) other relapsed or refractory AML.
  • Drug: IMGN632
    CD123-targeted ADC

Recruiting Locations

More Details

Status
Recruiting
Sponsor
ImmunoGen, Inc.

Study Contact

ImmunoGen Clinical Trials
781-895-0115
medicalaffairs@immunogen.com

Detailed Description

The study comprises a dose escalation phase followed by a dose expansion phase to further characterize the safety profile and confirm the MTD. IMGN632 will be administered IV on Day 1 of each cycle, with cycles repeating every 21 days. Treatment will continue for up to 2 cycles (6 weeks) in the absence of disease progression (PD), treatment intolerance, or withdrawal of consent.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.