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

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ClinicalTrials.gov Identifier: NCT03106428
Recruitment Status : Recruiting
First Posted : April 10, 2017
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 408 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 : March 29, 2017
Estimated Primary Completion Date : July 20, 2021
Estimated Study Completion Date : July 20, 2021


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




Primary Outcome Measures :
  1. Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of adverse events (AEs)

  2. Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of serious adverse events (SAEs)

  3. Occurrence of dose-limiting toxicities (DLTs) [ Time Frame: 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.

  4. Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent and up to 21 days post end of treatment ]
    To assess serum chemistry, hematology, Coagulation and urinalysis

  5. Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed consent and up to 21 days post end of treatment ]
    To assess body temperature, blood pressure, and heart rate

  6. Number of patients with changes in electrocardiogram (ECG) results from baseline [ Time Frame: From time of informed consent and up to 21 days post end of treatment ]
    To assess using twelve-lead ECG recordings

  7. Percentage of patients with changes in laboratory parameters from baseline [ Time Frame: 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 :
  1. MEDI7247 maximum observed concentration for PK [ Time Frame: From time of informed consent through 30 days post end of treatment ]
    To assess the Pharmacokinetics of MEDI7247

  2. MEDI7247 area under the concentration-time curve for PK [ Time Frame: From time of informed consent through 30 days post end of treatment ]
    To assess the Pharmacokinetics of MEDI7247

  3. MEDI7247 clearance for PK [ Time Frame: From time of informed consent through 30 days post end of treatment ]
    To assess the Pharmacokinetics of MEDI7247

  4. MEDI7247 terminal half-life for PK [ Time Frame: From time of informed consent through 30 days post end of treatment ]
    To assess the Pharmacokinetics of MEDI7247

  5. Number of subjects who develop anti-drug antibodies (ADAs) [ Time Frame: From time of informed consent through 30 days post end of treatment ]
    To assess the immunogenicity of MEDI7247

  6. Best overall response (BOR) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247

  7. Objective response rate (ORR) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247

  8. Time to response (TTR) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247

  9. Duration of response (DoR) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247

  10. Progression-free survival (PFS) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247

  11. Overall survival (OS) [ Time Frame: From time of informed consent and up to 3 years after final patient is enrolled ]
    To assess the anti-tumor activity of MEDI7247



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03106428


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 20 Study Locations
Sponsors and Collaborators
MedImmune LLC

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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03106428     History of Changes
Other Study ID Numbers: D8540C00001
First Posted: April 10, 2017    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MedImmune LLC:
MEDI7247
Acute Myeloid Leukemia
Multiple Myeloma
Diffuse Large B-cell Lymphoma
AML
MM
DLBCL

Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Leukemia
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma
Lymphatic Diseases