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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01460134
First received: October 12, 2011
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
CD27 Expressing B-cell Malignancies, (for Example
Chronic Lymphocytic Leukemia, Burkett's Lymphoma,
Mantle Cell Lymphoma, Primary Lymphoma of the Central Nervous System,
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)
Drug: CDX-1127
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • Characterize the adverse events associated with CDX-1127 administration [ Time Frame: Safety follow up is 70 days from last dose. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Until end of treatment ] [ Designated as safety issue: No ]
  • Levels of CDX-1127 in circulating blood. [ Time Frame: Until end of treatment ] [ Designated as safety issue: No ]
  • Activity Evaluations [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
    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) [ Time Frame: Until end of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: October 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematologic Malignancies (Dose Escalation)
B-Cell Enrollment Complete T-Cell Enrollment Ongoing
Drug: CDX-1127

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.

Experimental: Solid tumors (Dose Escalation; COMPLETED) Drug: CDX-1127

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.

Experimental: Solid Tumors (Expansion Phase)
Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma.
Drug: CDX-1127
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01460134

Locations
United States, Arizona
Mayo Clinic Arizona - Cancer Clinical Research Unit Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Charanjit Singh, CRC    480-301-6046    singh.charanjit@mayo.edu   
Principal Investigator: Donald Northfelt, MD         
United States, California
Stanford Cancer Center - Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Jennifer Vargas    650-723-0371    jennyv7@stanford.edu   
Principal Investigator: Branimir Sikic, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Stephen M. Ansell, M.D, Ph.D.         
United States, New York
Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine Recruiting
New York, New York, United States, 10029
Contact: Julia Howard    212-824-7822    julia.howard@mssm.edu   
Principal Investigator: Joshua Brody, MD         
United States, Ohio
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Cynthia Taylor, CCRC    614-293-2366    Cynthia.taylor@osumc.edu   
Contact: Jennifer Thurmond       jennifer.thurmond@osumc.edu   
Principal Investigator: William Carson, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Knight Clinical Trials Information Line    503-494-1080    trials@ohsu.edu   
Principal Investigator: Matthew H Taylor, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Drug Development Unit Referral Line    615-339-4214      
Principal Investigator: Howard Burris, MD         
United States, Texas
Mary Crowley Cancer Research Centers - Medical City Recruiting
Dallas, Texas, United States, 75230
Contact: Alyssa Roth, CRC    972-566-3061    aroth@marycrowley.org   
Principal Investigator: John J. Nemunaitis, MD         
United States, Virginia
University of Virginia Health System Active, not recruiting
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Celldex Therapeutics
  More Information

No publications provided

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT01460134     History of Changes
Other Study ID Numbers: CDX1127-01
Study First Received: October 12, 2011
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Celldex Therapeutics:
CD27 expressing Hematologic Malignancies
CD27 expressing Solid Tumors
solid tumor
ovarian cancer
non-small cell lung cancer
chronic lymphocytic leukemia
Burkett's lymphoma
mantle cell lymphoma
primary lymphoma of the central nervous system
marginal zone B cell lymphoma
metastatic melanoma
renal (clear) cell carcinoma
hormone-refractory prostate adenocarcinoma
colorectal adenocarcinoma

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Hematologic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Adenocarcinoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Melanoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell

ClinicalTrials.gov processed this record on August 21, 2014