A Multiple Ascending Dose Study of MEDI7247 in Participants with Selected Relapsed/Refractory Hematological Malignancies

Study identifier:D8540C00001

ClinicalTrials.gov identifier:NCT03106428

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Acute Myeloid Leukemia

Phase

Phase 1

Healthy volunteers

Study drug

MEDI7247

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 100 Years

Date

Study Start Date: 29 Mar 2017

Primary Completion Date: 03 Jan 2020

Study Completion Date: 03 Jan 2020

Study design

Allocation: Non-randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2020 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

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. Creatinine clearance (CrCL) >= 40 mL/min
6. Female participants 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 study drug.
7. Nonsterilized male participants 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 study drug.

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 natural killer (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. Participants who have previously received an autologous stem cell transplant (SCT), are excluded if less than 120 days have elapsed from the time of transplant or the participant 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. Participants at risk of non-disease related major bleeding (eg, recent gastrointestinal 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.

No locations available

Arms	Assigned Interventions
Experimental: AML: MEDI7247 Dose 2 Participants with acute myeloid leukemia (AML) will receive intravenous (IV) MEDI7247 Dose 2 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Dose 3 Participants with AML will receive IV MEDI7247 Dose 3 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Fractionated Dose 3 Participants with AML will receive IV MEDI7247 Dose 3 either on Days 1, 2, and 3 of each 21-day cycle or on Days 1, 8, 15 of each 28-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Dose 4 Participants with AML will receive IV MEDI7247 Dose 4 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Dose 5 Participants with AML will receive IV MEDI7247 Dose 5 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Dose 6 Participants with AML will receive IV MEDI7247 Dose 6 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: AML: MEDI7247 Dose 7 Participants with AML will receive IV MEDI7247 Dose 7 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: MM: MEDI7247 Fractionated Dose 1 Participants with multiple myeloma (MM) will receive IV MEDI7247 Dose 1 either on Days 1, 2, and 3 of each 21-day cycle or on Days 1, 8, 15 of each 28-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: MM: MEDI7247 Dose 2 Participants with MM will receive IV MEDI7247 Dose 2 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: MM: MEDI7247 Dose 4 Participants with MM will receive IV MEDI7247 Dose 4 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: MM: MEDI7247 Dose 5 Participants with MM will receive IV MEDI7247 Dose 5 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: MM: MEDI7247 Dose 6 Participants with MM will receive IV MEDI7247 Dose 6 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Dose 2 Participants with diffuse large B-cell lymphoma (DLBCL) will receive IV MEDI7247 Dose 2 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Dose 3 Participants with DLBCL will receive IV MEDI7247 Dose 3 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Fractionated Dose 3 Participants with DLBCL will receive IV MEDI7247 Dose 3 either on Days 1, 2, and 3 of each 21-day cycle or on Days 1, 8, 15 of each 28-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Dose 4 Participants with DLBCL will receive IV MEDI7247 Dose 4 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Dose 5 Participants with DLBCL will receive IV MEDI7247 Dose 5 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.
Experimental: DLBCL: MEDI7247 Dose 6 Participants with DLBCL will receive IV MEDI7247 Dose 6 on Day 1 of each 21-day cycle (for a maximum of 2 years) until unacceptable toxicity, documentation of disease progression, or development of other reason for treatment discontinuation.	Drug: MEDI7247 Participants with AML or MM or DLBCL will receive IV MEDI7247 doses.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]