Acute Myeloid Leukemia, Diffuse Large B-cell Lymphoma, Multiple Myeloma
Conditions
Keywords
MEDI7247, Acute Myeloid Leukemia, Multiple Myeloma, Diffuse Large B-cell Lymphoma, AML, MM, DLBCL
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.
Interventions
DRUGMEDI7247
The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| MEDI7247 maximum observed concentration for PK | From time of informed consent through 30 days post end of treatment | To assess the Pharmacokinetics 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 |
| 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 |
| 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 |
Countries
France, South Korea, United States
Outcome results
None listed