Clinical trial NCT01460134: A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma)
Any T-cell Malignancy
Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma
Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer
Colorectal Adenocarcinoma, Non-small Cell Lung Cancer)
Burkett's Lymphoma
Primary Lymphoma of the Central Nervous System
Keywords: CD27 expressing Hematologic Malignancies
CD27 expressing Solid Tumors
chronic lymphocytic leukemia
Burkett's lymphoma
mantle cell lymphoma
primary lymphoma of the central nervous system
marginal zone B cell lymphoma
solid tumor
metastatic melanoma
renal (clear) cell carcinoma
hormone-refractory prostate adenocarcinoma
ovarian cancer
colorectal adenocarcinoma
non-small cell lung cancer
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-10-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: CDX-1127 is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and also on certain hematologic tumor cells and may act to promote anti-tumor effects.

This study will evaluate the safety and activity of escalating doses of CDX-1127 in patients with B-cell and T-cell hematologic malignancies known to express CD27 and solid tumors that are more likely to be responsive to the immune system.

Eligible patients who enroll in the dose escalation portion of the study will be assigned to one of 5 dose levels of CDX-1127. This first phase of the study will test the safety profile of CDX-1127 and will assess which dose to test in future studies.

During the Expansion phase, cohorts of approximately 15 patients each will receive the study treatment to continue to evaluate the safety profile of CDX-1127 and to determine if it has an effect on their cancer. Expansion cohorts may be limited to one or more tumor types.

Patients enrolled in the study may receive study treatment for up to 5 cycles, until their disease has progressed or until it is necessary to stop the treatment for safety or other reasons.

All patients enrolled in the study will be closely monitored to determine if their cancer is responding to treatment and for any side effects that may occur.

Eligibility criteria: Inclusion Criteria:

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. 18 years of age or older.
2. Body Weight ≤ 120 kg.
3. 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.
4. 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.
5. Measurable or evaluable disease.
6. Have adequate blood, bone marrow, liver and kidney function as determined by laboratory tests.
7. If of childbearing potential (male or female), agree to practice an effective form of contraception during study treatment.
8. Have little or no side effects remaining from prior cancer therapies.
9. Provide written informed consent.

Exclusion Criteria:

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Known prior primary or metastatic brain or meningeal tumors.
2. Receiving treatment with immunosuppressive agents, including any systemic steroids.
3. Active infection requiring systemic therapy, known HIV infection, or positive test for hepatitis B surface antigen or hepatitis C.
4. Is being treated for anti-coagulation (i.e. warfarin) for reasons other than catheter patency.
5. Women who are pregnant or lactating.
6. Prior allogeneic bone marrow transplant.
7. Autologous bone marrow transplant within 100 days of first dosing.
8. Recent chemotherapy or other anti-cancer therapy (within 2 - 14 weeks depending on treatment type).
9. Systemic radiation therapy within 4 weeks or prior focal radiotherapy within 2 weeks prior to first dosing.

Primary outcomes:
measure: Characterize the adverse events associated with CDX-1127 administration
timeFrame: Safety follow up is 70 days from last dose.
Secondary outcomes:
measure: Levels of anti-CD27 antibodies in circulating blood.
timeFrame: Until end of treatment
measure: Levels of CDX-1127 in circulating blood.
timeFrame: Until end of treatment
measure: Activity Evaluations
timeFrame: Until disease progression
measure: Immune system effects (eg: lymphoid cell populations and serum cytokine levels)
timeFrame: Until end of treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona - Cancer Clinical Research Unit
state: Arizona
city: Stanford
country: United States
facility: Stanford Cancer Center - Stanford University
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers - Medical City
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
References:
citation: 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.
citation: Ansell 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.