A Phase 1, Multi-center, Open-label Study of IMGN779 Administered Intravenously in Adult Patients with Relapsed/Refractory CD33-positive Acute Myeloid Leukemia
You are being asked to take part in this study because you have leukemia that is refractory (has not responded to treatment) or relapsed (has come back after treatment). The goal of this clinical research study is to learn the highest tolerated dose of the experimental drug IMGN779 that can be given to patients with leukemia. The safety and effects of the drug will also be studied. Researchers also want to learn the best schedule by which the drug can be given. Participants receiving this consent form will receive the study drug every week (Schedule B). Participants receiving the other consent form will receive the study drug every 2 weeks (Schedule A). This is the first study using IMGN779 in humans.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: IMGN779
Treatment Location: Both at MDACC & and Other Sites
Sponsor: ImmunoGen, Inc.
Primary Objectives To determine the MTD and recommended dosing schedule of IMGN779 administered IV as single agent To determine the RP2D of IMGN779 when administered IV on the selected dosing schedule Secondary Objectives To characterize the safety profile and tolerability of IMGN779 when given as a single agent To characterize the PK profile of IMGN779 To evaluate the potential immunogenicity of IMGN779 To assess evidence of anti-tumor activity Exploratory Objectives To characterize the Pd profile of IMGN779 by assessing: CD33 receptor availability Additional biomarkers associated with AML and oncogenic pathways To correlate CD33 antigen density and molecular characterization of disease to response To explore mechanisms of IMGN779 acquired resistance through analysis of CD33 expression and molecular changes in relapsing disease To evaluate other potential predictive and prognostic biomarkers
IRB Review and Approval Date: 03/31/2016
Recruitment Status: Open
Projected Accrual: 124
1) *Disease Characteristics and allowable prior therapy: a. Dose
Escalation - Patients with relapsed or refractory AML (excluding acute
promyelocytic leukemia), based on World Health Organization
Classification; Relapsed/refractory AML is defined as 1) primary
induction failure after two or more cycles of chemotherapy; 2) first
early relapse after a remission duration of fewer than six months; and
3) second or subsequent relapse. b. Dose Expansion - Patients with AML
at first relapse. AML at first relapse is defined as disease that has
relapsed more than 6 months after initial remission. *Note - patients
with secondary AML or antecedent MDS will be eligible in all stages of
2) Morphological evidence of CD33-positive AML (with at least 20% of blasts being CD33-positive) by flow cytometry analysis performed at a local CLIA-certificed laboratory.
3) Age >/= 18 years old.
4) ECOG performance status </= 2.
5) Previous treatment-related adverse events must have resolved to </= Grade 1 (excluding alopecia).
6) WBC </= 20,000/uL (use of hydroxyurea or leukapheresis to manage WBC count is permitted).
7) Liver enzymes (AST and ALT) </= 2.5 x the upper limits of normal (ULN). Exceptions may be made for patients with elevated liver transaminases secondary to AML.
8) Total bilirubin </=1.5 x ULN within 14 days of enrollment.
9) Serum creatinine </= 2 mg/dL within 14 days of enrollment.
10) Left ventricular ejection fraction (LVEF) greater than 50%.
11) Patients with a prior autologous and/or allogeneic bone marrow transplant are eligible for the dose escalation phase ONLY. Patients with an allogeneic transplant must meet the following conditions: the transplant must have been performed more than 120 days before registration to this study; patients must not have active >/= Grade 2 acute graft versus host disease (GvHD), moderate or severe limited chronic GvHD, or extensive chronic GvHD of any severity; patients must be off all immunosuppression for at least two weeks. The use of topical steroids for cutaneous manifestations of GvHD is allowed.
12) Patients who have previously received anti-CD33 directed therapy will be eligible to enroll in the dose escalation portion of the study ONLY.
13) Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
14) 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 effective contraceptive methods (e.g., oral, parenteral, or implantable hormonal contraceptive, intra-uterine device, barrier contraceptive with spermicide, partner’s latex condom or vasectomy) while on study drug and for at least 12 weeks after the last dose of study drug.
15) WCBP must have a negative pregnancy test documented within three days prior to the first dose of study drug.
16) Male patients must agree to use a latex condom even if they have had a successful vasectomy and continue to follow these requirements for at least 12 weeks following the last dose of study drug.
17) Patients with prior malignancies are eligible; however, patients must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy for the prior malignancy at least six months prior to their registration on this study. In addition, all treatment-related toxicities must have resolved. Patients with a history of non-melanoma skin cancer, in-situ breast or cervical cancer, which has been excised, are eligible.
1) Patients with previously untreated AML.
2) Any concurrent anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational agents (with the exception of hydroxyurea or leukapheresis for control of hyperleukocytosis) within 14 days or 5 half-lives of drugs, whichever is shorter, prior to Cycle 1 Day 1.
3) Extramedullary disease ONLY (i.e. without bone marrow involvement).
4) Myocardial infarction within six months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically-significant conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at Screening must be documented by the investigator as not medically relevant.
5) Corrected QT interval (QTc) > 480 msec.
6) Presence of serious or poorly controlled medical conditions that in the opinion of the investigator puts the patient under undue risk.
7) Uncontrolled, active infection including known active hepatitis B or C, Human Immunodeficiency Virus (HIV) infection, cytomegalovirus (CMV) infection or any other known concurrent infectious disease.
8) AML patients with known, active leptomeningeal/central nervous system (CNS) involvement (lumbar puncture (LP) is not required unless clinically indicated); patients with history of CNS involvement may be enrolled if they have been successfully treated and two subsequent, consecutive LPs were negative.
9) Prior hypersensitivity to monoclonal antibodies.
10) Patients who have undergone a major surgery within four weeks prior to study enrollment.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
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