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

This study is currently recruiting participants.
Verified December 2012 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01460134
First received: October 12, 2011
Last updated: December 4, 2012
Last verified: December 2012
  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
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
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:
  • Number of reported adverse events [ Time Frame: Until day 70 follow up. ] [ Designated as safety issue: Yes ]
    The number 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 day 70 follow up ] [ Designated as safety issue: No ]
  • Levels of CD27 in circulating blood [ Time Frame: Until day 70 of follow up ] [ Designated as safety issue: No ]
  • Activity Evaluations [ Time Frame: Until day 70 of follow up ] [ 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, serum cytokines, and response to recall antigens and vaccination). [ Time Frame: Until day 70 of follow up ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: October 2011
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematologic Malignancies
This Phase 1 dose-escalation safety and PK study will be conducted in patients with hematologic malignancies known to express CD27
Drug: CDX-1127

Patients will initially receive a single dose of CDX 1127, followed by a 28-day observation period and a Multiple-Dose Phase (one "cycle" of 4 weekly doses of CDX-1127). Patients enrolled into the expansion cohort(s) will start treatment with the multi-dose phase. All patients with stable disease who do not experience 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
This Phase 1 dose-escalation safety and PK study will be conducted in patients with solid tumors which express CD27.
Drug: CDX-1127

Patients will initially receive a single dose of CDX 1127, followed by a 28-day observation period and a Multiple-Dose Phase (one "cycle" of 4 weekly doses of CDX-1127). Patients enrolled into the expansion cohort(s) will start treatment with the multi-dose phase. All patients with stable disease who do not experience 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.


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 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 study will be assigned to one of 5 dose levels of CDX-1127. The 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 second phase, up to 30 patients 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. 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 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
  4. Tumor must be recurrent or treatment refractory with no remaining alternative, approved therapy options
  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
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, 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, 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 Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Sasha White     434-982-1902     SNW2Z@virginia.edu    
Contact: Kristy Scott, BS     434-982-6714     KS4WW@virginia.edu    
Principal Investigator: Geoffrey R Weiss, MD            
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: December 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Celldex Therapeutics:
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

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Mucinous
Neoplasms
Carcinoma
Prostatic Neoplasms
Carcinoma, Non-Small-Cell Lung
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lung Neoplasms
Lymphoma
Melanoma
Ovarian Neoplasms
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Hematologic Neoplasms
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Cystic, Mucinous, and Serous
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on May 22, 2013