Clinical Trial - NCT03106428

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

Recruiting

Sponsor: MedImmune LLC

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03106428

Protocol Info

Short Description: MEDI7247 IN HEMATOLOGICAL MALIGNANCIES
Long Description: A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activityof MEDI7247 in Patients with Selected Relapsed/Refractory Hematological Malignancies
MGH Status: Open
Sponsor: MED Immune
Disease Program: Leukemia

Next Steps


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Purpose

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 Title Intervention Phase
Acute Myeloid Leukemia Multiple Myeloma Diffuse Large B-cell Lymphoma MEDI7247 Phase 1
Study Type Interventional
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

Primary Outcome Measures

Occurrence of adverse events (AEs) [Time Frame: From time of informed consent through 90 days post end of treatment] [Designated as safety issue: ]

Occurrence of serious adverse events (SAEs) [Time Frame: From time of informed consent through 90 days post end of treatment] [Designated as safety issue: ]

Occurrence of dose-limiting toxicities (DLTs) [Time Frame: During the evaluation period of 21 or 42 days post-first dose] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

MEDI7247 maximum observed concentration for PK [Time Frame: From time of informed consent through 30 days post end of treatment] [Designated as safety issue: ]

MEDI7247 area under the concentration-time curve for PK [Time Frame: From time of informed consent through 30 days post end of treatment] [Designated as safety issue: ]

MEDI7247 clearance for PK [Time Frame: From time of informed consent through 30 days post end of treatment] [Designated as safety issue: ]

MEDI7247 terminal half-life for PK [Time Frame: From time of informed consent through 30 days post end of treatment] [Designated as safety issue: ]

Number of subjects who develop anti-drug antibodies (ADAs) [Time Frame: From time of informed consent through 30 days post end of treatment] [Designated as safety issue: ]

Best overall response (BOR) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Objective response rate (ORR) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Time to response (TTR) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Duration of response (DoR) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Progression-free survival (PFS) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: From time of informed consent and up to 3 years after final patient is enrolled] [Designated as safety issue: ]

Estimated Enrollment: 408
Study Start Date: March 2017
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: July 2021
Arms Assigned Interventions

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.

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.

Eligibility

Ages Eligible for Study: 100 Years-100 Years

Genders Eligible for Study: All

Accepts Healthly 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03106428

Locations

  • United States, Arkansas
    • Research Site Little Rock, Arkansas, United States, 72205
  • United States, California
    • Research Site Los Angeles, California, United States, 90095
  • United States, Colorado
    • Research Site Denver, Colorado, United States, 80218
  • United States, Georgia
    • Research Site Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • Research Site Chicago, Illinois, United States, 60611
  • United States, Massachusetts
    • Research Site Boston, Massachusetts, United States, 02114
    • Research Site Boston, Massachusetts, United States, 02114
  • United States, Missouri
    • Research Site Saint Louis, Missouri, United States, 63110
  • United States, New York
    • Research Site New York, New York, United States, 10065
  • United States, South Carolina
    • Research Site Greer, South Carolina, United States, 29650
  • United States, Tennessee
    • Research Site Nashville, Tennessee, United States, 37203
  • United States, Texas
    • Research Site Houston, Texas, United States, 77030
    • Research Site San Antonio, Texas, United States, 78229
  • United States, Washington
    • Research Site Seattle, Washington, United States, 98195
  • Canada, Ontario
    • Research Site Toronto, Ontario, Canada, M5G 2M9
  • France,
    • Research Site Pierre Benite, , France, 69495
    • Research Site Villejuif, , France, 94805
  • Korea, Republic of,
    • Research Site Seoul, , Korea, Republic of, 03080
    • Research Site Seoul, , Korea, Republic of, 06351

Sponsors and Collaborators

MedImmune LLC

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03106428
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by MedImmune LLC:

MEDI7247

Acute Myeloid Leukemia

Multiple Myeloma

Diffuse Large B-cell Lymphoma

AML

MM

DLBCL

Additional relevant MeSH terms:

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, B-Cell

Lymphoma, Large B-Cell, Diffuse

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019