A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

To assess safety and tolerability, describe the dose-limiting toxicities, determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and a recommended dose for further evaluation of MEDI7247 in patients with selected hematological malignancies who have relapsed after, or are refractory to prior standard therapy, and for whom there is no standard salvage regimen available.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Multiple Myeloma; Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: MEDI7247

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Pierre Benite, France, 69495
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
2. Age ≥ 18 years at the time of screening.
3. Written informed consent and any locally required authorization
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Liver Function Tests: AST and ALT ≤ 3 × ULN, and serum TBL ≤ 1.5 × ULN, unless consistent with Gilbert's syndrome for which TBL ≤ 2.5 × ULN is allowed.

5. CrCL ≥ 40 mL/min 6. Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from 7 days post-screening, and must agree to continue using such precautions for 90 days after the last dose of investigational product.

7. Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.

Exclusion Criteria:

1. Received cytotoxic chemotherapy within 21 days (or 42 days for nitrosureas or mitomycin C) prior to the first scheduled dose of MEDI7247.
2. Received major surgery (as defined by the Investigator), radiotherapy, or immunotherapy (including immune checkpoint inhibitors and adoptive cellular therapy such as autologous or donor NK cell or T lymphocyte infusions (e.g. CAR -T cells)) within 28 days of the first scheduled dose of MEDI7247.
3. Received an investigational drug within 14 days of the first scheduled dose of MEDI7247 or not recovered from associated toxicities.
4. Patients who have previously received an autologous SCT, are excluded if less than 120 days have elapsed from the time of transplant or the patient has not recovered from transplant-associated toxicities prior to the first scheduled dose of MEDI7247.
5. History of liver cirrhosis, liver fibrosis or prior liver irradiation regardless of the time interval (not including total body irradiation administered during allogeneic SCT).
6. Failure to recover from all prior treatment-related non-hematological toxicities to ≤ Grade 1 prior to the first scheduled dose of MEDI7247 (except for alopecia and neuropathy).
7. Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).
8. Current severe active systemic disease including active concurrent malignancy
9. Central nervous system (CNS) disease that is untreated, symptomatic, or requires therapy to control symptoms.
10. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: acute myeloid leukemia; Patients with R/R AML by World Health Organization (WHO) classification (Arber et al, 2016) who have failed prior standard therapy and for whom no standard therapies are available	Drug: MEDI7247; The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV
EXPERIMENTAL: Multiple Myeloma; Patients with R/R MM who have failed prior standard therapy(ies) which should include immunomodulatory agents and proteasome inhibitors and for whom there is no standard salvage regimen.	Drug: MEDI7247; The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV
EXPERIMENTAL: Diffuse Large B-cell Lymphoma; Patients with R/R DLBCL who have failed prior standard therapy(ies) and for whom there is no standard salvage regimen.	Drug: MEDI7247; The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events (AEs)	To assess by the occurrence of adverse events (AEs)	From time of informed consent through 90 days post end of treatment
Occurrence of serious adverse events (SAEs)	To assess by the occurrence of serious adverse events (SAEs)	From time of informed consent through 90 days post end of treatment
Occurrence of dose-limiting toxicities (DLTs)	To assess by the occurrence of non-Hematologic and hematologic toxicities, AEs, and abnormal laboratory results.	During the evaluation period of 21 or 42 days post-first dose
Number of patients with changes in laboratory parameters from baseline	To assess serum chemistry, hematology, Coagulation and urinalysis	From time of informed consent and up to 21 days post end of treatment
Number of patients with changes in vital signs from baseline	To assess body temperature, blood pressure, and heart rate	From time of informed consent and up to 21 days post end of treatment
Number of patients with changes in electrocardiogram (ECG) results from baseline	To assess using twelve-lead ECG recordings	From time of informed consent and up to 21 days post end of treatment
Percentage of patients with changes in laboratory parameters from baseline	To assess serum chemistry, hematology, Coagulation and urinalysis	From time of informed consent and up to 21 days post end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MEDI7247 maximum observed concentration for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
MEDI7247 area under the concentration-time curve for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
MEDI7247 clearance for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
MEDI7247 terminal half-life for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
Number of subjects who develop anti-drug antibodies (ADAs)	To assess the immunogenicity of MEDI7247	From time of informed consent through 30 days post end of treatment
Best overall response (BOR)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled
Objective response rate (ORR)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled
Time to response (TTR)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled
Duration of response (DoR)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled
Progression-free survival (PFS)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled
Overall survival (OS)	To assess the anti-tumor activity of MEDI7247	From time of informed consent and up to 3 years after final patient is enrolled

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2017
• Primary Completion (ACTUAL): January 3, 2020
• Study Completion (ACTUAL): January 3, 2020

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (ACTUAL): April 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Multiple Myeloma; DLBCL; AML; MM; Diffuse Large B-cell Lymphoma; MEDI7247
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Multiple Myeloma; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: D8540C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No