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Clinical Trial 19870

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03386513

Phase: Phase I
Principal Investigator: Sweet, Kendra

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Overview

Study Title

A Phase 1, Multi-center, Open-label Study of IMGN632 Administered Intravenously in Patients with Relapsed/Refractory CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies

Summary

The purpose of this study is to determine the Maximum Tolerated Dose (MTD) and assess the safety, tolerability, PK, immunogenicity, and preliminary anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.

Objective

To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of IMGN632 on the selected dosing schedule(s) (dose escalation) To assess the anti-leukemia activity in BPDCN patients (tumor-specific expansion cohort)

Treatments

Therapies

Immunotherapy

Medications

IMGN632 ()

Inclusion Criteria

Inclusion Criteria:

  • 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.
  • Dose Escalation – Relapsed or refractory AML (excluding acute promyelocytic leukemia) or BPDCN, based on World Health Organization Classification (see Appendix E for definition of clinical relapse).
  • Dose Expansion: Cohort #1: Patients with relapsed or refractory BPDCN 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: 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 in the BPDCN who have not received prior systemic therapy. Note: Patients in the BPDCN Expansion phase cohort #1 may have received up to 3 prior lines of systemic therapy (regardless of tagraxofusp-erz exposure)
  • 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status at least 1. If nonambulatory due to a chronic disability, must be Karnofsky performance status > 70.
  • Previous treatment related toxicities must have resolved to Grade 1 (excluding alopecia).
  • Laboratory values per protocol
  • Estimated glomerular filtration rate (eGFR) of greater than 30 mL/min/1.73m^2 or creatine clearance of greater than 30mL/min
  • Left ventricular ejection fraction greater than or equal to 45%
  • 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 ≥ 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 prior to first dose of IMGN632.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
  • Women of child bearing potential (WCBP), 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 (i.e., 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 12 weeks after the last dose of study drug.
  • WCBP must have a negative pregnancy test prior to the first dose of study drug.
  • Male patients who are able to father children must agree to use an effective method of contraception even if they have had a successful vasectomy throughout the study and for at least 4 months after the last dose of IMGN632.
  • Other criteria may apply

    • Exclusion Criteria

    Exclusion Criteria:

  • Participants who, in the judgment of their treating physician, have available standard of care therapies will be excluded from Cohorts 1 through 5.
  • Frontline BPDCN patients with active 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 or must have been treated locally, have at least 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.
  • History of venocclusive disease of the liver.
  • History of Grade 4 capillary leak syndrome, or non-cardiac Grade 4 edema are ineligible, eg, related to tagraxofusp-erz or other etiology.
  • Corrected QT interval (QTc Fridericia formula) > 480 msec.
  • Myocardial infarction within 6 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.
  • Interval from prior cancer therapy: (a) For frontline BPDCN patients with local therapy (e.g., radiotherapy) patients must not have received treatment within 14 days prior to drug administration on this study. (b) 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.
  • 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).
  • Patients who have undergone a major surgery within 4 weeks prior to study enrollment (or longer if not fully recovered).
  • 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 judgement of the Investigator
  • Other exclusions may apply

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