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A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

Primary Purpose

CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CDX-1127

About this trial

This is an interventional treatment trial for CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

18 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.

Exclusion Criteria:

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.

Sites / Locations

Mayo Clinic Arizona - Cancer Clinical Research Unit
Stanford Cancer Center - Stanford University
Mayo Clinic
Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine
The Ohio State University Comprehensive Cancer Center
Oregon Health and Science University
University of Pennsylvania Abramson Cancer Center
Sarah Cannon Research Institute
Mary Crowley Cancer Research Centers - Medical City
University of Virginia Health System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Hematologic Malignancies (Dose Escalation)

Solid tumors (Dose Escalation; COMPLETED)

Solid Tumors (Expansion Phase; COMPLETED)

Hematologic Malignancies (COMPLETED)

Arm Description

B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED

Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma.

Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Levels of anti-CD27 antibodies in circulating blood.

Levels of CDX-1127 in circulating blood.

Activity Evaluations

Determine the anti-malignant cell activity of CDX-1127 based on change from baseline in tumor measurements every 12 weeks.

Immune system effects (eg: lymphoid cell populations and serum cytokine levels)

Full Information

NCT ID

NCT01460134

First Posted

October 12, 2011

Last Updated

January 29, 2018

Sponsor

Celldex Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT01460134

Brief Title

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

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

October 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celldex Therapeutics

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hematologic Malignancies (Dose Escalation)

Arm Type

Experimental

Arm Description

B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED

Arm Title

Solid tumors (Dose Escalation; COMPLETED)

Arm Type

Experimental

Arm Title

Solid Tumors (Expansion Phase; COMPLETED)

Arm Type

Experimental

Arm Description

Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma.

Arm Title

Hematologic Malignancies (COMPLETED)

Arm Type

Experimental

Arm Description

Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma.

Intervention Type

Drug

Intervention Name(s)

CDX-1127

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

CDX-1127

Intervention Description

Patients will receive 4 weekly doses of CDX-1127 followed by an observation period. 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.

Intervention Type

Drug

Intervention Name(s)

CDX-1127

Intervention Description

Patients will receive four doses of CDX-1127 administered every three weeks followed by an observation period. 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.

Primary Outcome Measure Information:

Title

Characterize the adverse events associated with CDX-1127 administration

Description

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.

Time Frame

Safety follow up is 70 days from last dose.

Secondary Outcome Measure Information:

Title

Levels of anti-CD27 antibodies in circulating blood.

Time Frame

Until end of treatment

Title

Levels of CDX-1127 in circulating blood.

Time Frame

Until end of treatment

Title

Activity Evaluations

Description

Determine the anti-malignant cell activity of CDX-1127 based on change from baseline in tumor measurements every 12 weeks.

Time Frame

Until disease progression

Title

Immune system effects (eg: lymphoid cell populations and serum cytokine levels)

Time Frame

Until end of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Among other criteria, patients must meet the following conditions to be eligible for the study: 18 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. Exclusion Criteria: 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.

Facility Information:

Facility Name

Mayo Clinic Arizona - Cancer Clinical Research Unit

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Stanford Cancer Center - Stanford University

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

The Ohio State University Comprehensive Cancer Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Oregon Health and Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

University of Pennsylvania Abramson Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Mary Crowley Cancer Research Centers - Medical City

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

University of Virginia Health System

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22908

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

28463630

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. Erratum In: J Clin Oncol. 2019 Feb 1;37(4):359.

Results Reference

background

PubMed Identifier

32380537

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.

Results Reference

derived

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A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

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