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

Sponsor

MedImmune LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT03106428

Collaborator

(none)

Enrollment

Locations

Arms

33.2

Actual Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Multiple Myeloma Diffuse Large B-cell Lymphoma	Drug: MEDI7247	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 29, 2017

Actual Primary Completion Date :

Jan 3, 2020

Actual Study Completion Date :

Jan 3, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
Age ≥ 18 years at the time of screening.
Written informed consent and any locally required authorization
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
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.
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.
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:

Received cytotoxic chemotherapy within 21 days (or 42 days for nitrosureas or mitomycin C) prior to the first scheduled dose of MEDI7247.
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.
Received an investigational drug within 14 days of the first scheduled dose of MEDI7247 or not recovered from associated toxicities.
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.
History of liver cirrhosis, liver fibrosis or prior liver irradiation regardless of the time interval (not including total body irradiation administered during allogeneic SCT).
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).
Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).
Current severe active systemic disease including active concurrent malignancy
Central nervous system (CNS) disease that is untreated, symptomatic, or requires therapy to control symptoms.
Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90095
2	Research Site	Denver	Colorado	United States	80218
3	Research Site	Atlanta	Georgia	United States	30322
4	Research Site	Chicago	Illinois	United States	60611
5	Research Site	Boston	Massachusetts	United States	02114
6	Research Site	Saint Louis	Missouri	United States	63110
7	Research Site	New York	New York	United States	10065
8	Research Site	Greer	South Carolina	United States	29650
9	Research Site	Nashville	Tennessee	United States	37203
10	Research Site	San Antonio	Texas	United States	78229
11	Research Site	Pierre Benite		France	69495
12	Research Site	Villejuif		France	94805
13	Research Site	Seoul		Korea, Republic of	03080
14	Research Site	Seoul		Korea, Republic of	06351