Clinical trial NCT03106428: A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Multiple Myeloma
Diffuse Large B-cell Lymphoma
Keywords: MEDI7247
Acute Myeloid Leukemia
Multiple Myeloma
Diffuse Large B-cell Lymphoma
AML
MM
DLBCL
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-04-10
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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. 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.

Primary outcomes:
measure: Occurrence of adverse events (AEs)
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of serious adverse events (SAEs)
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of dose-limiting toxicities (DLTs)
timeFrame: During the evaluation period of 21 or 42 days post-first dose
measure: Number of patients with changes in laboratory parameters from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
measure: Number of patients with changes in vital signs from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
measure: Number of patients with changes in electrocardiogram (ECG) results from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
measure: Percentage of patients with changes in laboratory parameters from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
Secondary outcomes:
measure: MEDI7247 maximum observed concentration for PK
timeFrame: From time of informed consent through 30 days post end of treatment
measure: MEDI7247 area under the concentration-time curve for PK
timeFrame: From time of informed consent through 30 days post end of treatment
measure: MEDI7247 clearance for PK
timeFrame: From time of informed consent through 30 days post end of treatment
measure: MEDI7247 terminal half-life for PK
timeFrame: From time of informed consent through 30 days post end of treatment
measure: Number of subjects who develop anti-drug antibodies (ADAs)
timeFrame: From time of informed consent through 30 days post end of treatment
measure: Best overall response (BOR)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
measure: Objective response rate (ORR)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
measure: Time to response (TTR)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
measure: Duration of response (DoR)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
measure: Progression-free survival (PFS)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
measure: Overall survival (OS)
timeFrame: From time of informed consent and up to 3 years after final patient is enrolled
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Greer
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Pierre Benite
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
Study officials:
References: