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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03106428
• Other study ID #: D8540C00001
• Status: Completed
• Phase: Phase 1
• Start date: March 29, 2017
• Est. completion date: January 3, 2020

Study information

• Verified date: February 2020
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: January 3, 2020
• Est. primary completion date: January 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Diffuse Large B-cell Lymphoma
• Leukemia, Myeloid, Acute
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Multiple Myeloma

Intervention

Drug:
• MEDI7247
The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV

Locations

Country	Name	City	State
France	Research Site	Pierre Benite
France	Research Site	Villejuif
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
United States	Research Site	Atlanta	Georgia
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Denver	Colorado
United States	Research Site	Greer	South Carolina
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	MEDI7247 maximum observed concentration for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
Secondary	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
Secondary	MEDI7247 clearance for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
Secondary	MEDI7247 terminal half-life for PK	To assess the Pharmacokinetics of MEDI7247	From time of informed consent through 30 days post end of treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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