CD27 Expressing B-cell Malignancies for Example Hodgkin's LymphomaPhase 1NCT01460134
A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers
A Phase 1 study testing CDX-1127 in people with CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, run by Celldex Therapeutics at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
- What is being tested?
- CDX-1127
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 10 sitesUnited States
- Study dates
- Oct 2011to 16 Oct 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Virginia Health System
Charlottesville, Virginia, 22908
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, 75230
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine
New York, New York, 10029
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic Arizona - Cancer Clinical Research Unit
Scottsdale, Arizona, 85259
Stanford Cancer Center - Stanford University
Stanford, California, 94305
About this study
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
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.
Read the 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.
- 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
- Being tested
- CDX-1127
- 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
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Melanoma, Margins of Excision, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDX-1127Drug
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.
CDX-1127Drug
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.
CDX-1127Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Hematologic Malignancies (Dose Escalation) | Experimental | B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED Receives: Drug: CDX-1127 |
| Solid tumors (Dose Escalation; COMPLETED) | Experimental | Not described Receives: Drug: CDX-1127 |
| Solid Tumors (Expansion Phase; COMPLETED) | Experimental | Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma. Receives: Drug: CDX-1127 |
| Hematologic Malignancies (COMPLETED) | Experimental | Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma. Receives: Drug: CDX-1127 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Safety follow up is 70 days from last dose.
Secondary outcomes (4)
Levels of anti-CD27 antibodies in circulating blood.
Measured: Until end of treatment
Levels of CDX-1127 in circulating blood.
Measured: Until end of treatment
Activity Evaluations
Determine the anti-malignant cell activity of CDX-1127 based on change from baseline in tumor measurements every 12 weeks.
Measured: Until disease progression
Immune system effects (eg: lymphoid cell populations and serum cytokine levels)
Measured: Until end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2015
- Study completion16 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CD27 Expressing B-cell Malignancies for Example Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01460134
- Sponsor's protocol ID
- CDX1127-01
- Status last verified
- Aug 2017
- First submitted
- 12 Oct 2011
- Last updated
- 31 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28463630Ansell 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.
PubMed 32380537
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01460134
- Acronym / sponsor ID
- CDX1127-01
- 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
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- 16 Oct 2017 (actual)
- First posted
- 26 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Hematologic Malignancies (Dose Escalation) | Experimental | Drug: CDX-1127B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED |
| Solid tumors (Dose Escalation; COMPLETED) | Experimental | Drug: CDX-1127 |
| Solid Tumors (Expansion Phase; COMPLETED) | Experimental | Drug: CDX-1127Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma. |
| Hematologic Malignancies (COMPLETED) | Experimental | Drug: CDX-1127Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CDX-1127Patients 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. | Drug | Hematologic Malignancies (Dose Escalation), Solid tumors (Dose Escalation; COMPLETED) |
| CDX-1127Patients 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. | Drug | Solid Tumors (Expansion Phase; COMPLETED) |
| CDX-1127Patients 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. | Drug | Hematologic Malignancies (COMPLETED) |
Primary outcome
Characterize the adverse events associated with CDX-1127 administration
Time frame: Safety follow up is 70 days from last dose.
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.
4 secondary outcomes
Levels of anti-CD27 antibodies in circulating blood.
Time frame: Until end of treatment
Levels of CDX-1127 in circulating blood.
Time frame: Until end of treatment
Activity Evaluations
Time frame: Until disease progression
Immune system effects (eg: lymphoid cell populations and serum cytokine levels)
Time frame: Until end of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- Background: PubMed 28463630Burris 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.
- Derived from this study: PubMed 32380537Ansell 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CDX-1127 in people with CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, run by Celldex Therapeutics at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterize the adverse events associated with CDX-1127 administration (time frame: Safety follow up is 70 days from last dose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01460134, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2018.