A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers
A Phase 1, Open-label, Dose-escalation, Safety and Pharmacokinetic Study of CDX-1127 in Patients With Selected Refractory or Relapsed Hematologic Malignancies or Solid Tumors
1 other identifier
interventional
90
1 country
10
Brief Summary
This is a study of CDX-1127, a therapy that targets the immune system and may act to promote anti-cancer effects. The study enrolls patients with hematologic cancers (certain leukemias and lymphomas), as well as patients with select types of solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2011
Longer than P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2011
CompletedFirst Submitted
Initial submission to the registry
October 12, 2011
CompletedFirst Posted
Study publicly available on registry
October 26, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 16, 2017
CompletedJanuary 31, 2018
August 1, 2017
4.2 years
October 12, 2011
January 29, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Characterize the adverse events associated with CDX-1127 administration
Analysis of adverse events along with the results of vital sign measurements, physical examinations, and clinical laboratory tests will be used to determine the safety profile of CDX-1127.
Safety follow up is 70 days from last dose.
Secondary Outcomes (4)
Levels of anti-CD27 antibodies in circulating blood.
Until end of treatment
Levels of CDX-1127 in circulating blood.
Until end of treatment
Activity Evaluations
Until disease progression
Immune system effects (eg: lymphoid cell populations and serum cytokine levels)
Until end of treatment
Study Arms (4)
Hematologic Malignancies (Dose Escalation)
EXPERIMENTALB-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED
Solid tumors (Dose Escalation; COMPLETED)
EXPERIMENTALSolid Tumors (Expansion Phase; COMPLETED)
EXPERIMENTALSeveral expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma.
Hematologic Malignancies (COMPLETED)
EXPERIMENTALSeveral expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma.
Interventions
Patients will initially receive a single dose of CDX-1127, followed by a 28-day observation period and a Multi-Dose Phase (one "cycle" of 4 weekly doses of CDX-1127). All patients with stable disease who do not experience a DLT or start alternate anti-cancer treatments may then be eligible for a Retreatment Phase (up to 4 additional "cycles"). Patients with confirmed partial response or complete response will be followed for response duration and may be eligible for additional cycles of treatment at the time of relapse/progression. The dose of CDX-1127 given for the Dose Escalation phase will depend on the cohort each patient is assigned to, and will range between 0.1 and 10.0 mg/kg of CDX-1127.
Eligibility Criteria
You may qualify if:
- Among other criteria, patients must meet the following conditions to be eligible for the study:
- years of age or older.
- Body Weight ≤ 120 kg.
- Histologic diagnosis of either a B-cell or T-cell hematologic malignancy known to express CD27 or one of the following solid tumors: metastatic melanoma, renal (clear) cell carcinoma, hormone-refractory prostate adenocarcinoma, ovarian cancer, colorectal adenocarcinoma or non-small cell lung cancer. For the solid tumor expansion cohorts, enrollment is limited to the following solid tumors: melanoma and renal cell carcinoma.
- Tumor must be recurrent or treatment refractory with no remaining alternative, approved therapy options, with the following exception: melanoma patients enrolled in the expansion phase must have previously received ipilimumab and, for patients with the BRAF V600E mutation, vemurafenib, or have been offered such therapies and refused, and patients must have progressive disease subsequent to previous therapies.
- Measurable or evaluable disease.
- Have adequate blood, bone marrow, liver and kidney function as determined by laboratory tests.
- If of childbearing potential (male or female), agree to practice an effective form of contraception during study treatment.
- Have little or no side effects remaining from prior cancer therapies.
- Provide written informed consent.
You may not qualify if:
- Among other criteria, patients who meet the following conditions are NOT eligible for the study:
- Known prior primary or metastatic brain or meningeal tumors.
- Receiving treatment with immunosuppressive agents, including any systemic steroids.
- Active infection requiring systemic therapy, known HIV infection, or positive test for hepatitis B surface antigen or hepatitis C.
- Is being treated for anti-coagulation (i.e. warfarin) for reasons other than catheter patency.
- Women who are pregnant or lactating.
- Prior allogeneic bone marrow transplant.
- Autologous bone marrow transplant within 100 days of first dosing.
- Recent chemotherapy or other anti-cancer therapy (within 2 - 14 weeks depending on treatment type).
- Systemic radiation therapy within 4 weeks or prior focal radiotherapy within 2 weeks prior to first dosing.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Mayo Clinic Arizona - Cancer Clinical Research Unit
Scottsdale, Arizona, 85259, United States
Stanford Cancer Center - Stanford University
Stanford, California, 94305, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine
New York, New York, 10029, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, 75230, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Related Publications (2)
Burris HA, Infante JR, Ansell SM, Nemunaitis JJ, Weiss GR, Villalobos VM, Sikic BI, Taylor MH, Northfelt DW, Carson WE 3rd, Hawthorne TR, Davis TA, Yellin MJ, Keler T, Bullock T. Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors. J Clin Oncol. 2017 Jun 20;35(18):2028-2036. doi: 10.1200/JCO.2016.70.1508. Epub 2017 May 2.
PMID: 28463630BACKGROUNDAnsell SM, Flinn I, Taylor MH, Sikic BI, Brody J, Nemunaitis J, Feldman A, Hawthorne TR, Rawls T, Keler T, Yellin MJ. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies. Blood Adv. 2020 May 12;4(9):1917-1926. doi: 10.1182/bloodadvances.2019001079.
PMID: 32380537DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 12, 2011
First Posted
October 26, 2011
Study Start
October 1, 2011
Primary Completion
December 1, 2015
Study Completion
October 16, 2017
Last Updated
January 31, 2018
Record last verified: 2017-08