Overview

This trial is active, not recruiting.

Conditions cd27 expressing b-cell malignancies, (for example: hodgkin's lymphoma,, 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)
Treatments cdx-1127
Phase phase 1
Target CD27
Sponsor Celldex Therapeutics
Start date October 2011
End date December 2015
Trial size 90 participants
Trial identifier NCT01460134, CDX1127-01

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
B-Cell Enrollment COMPLETED T-Cell Enrollment COMPLETED
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)
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)
Several expansion cohorts of up to 15 patients each are planned, including melanoma and renal cell carcinoma.
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.
(Experimental)
Several expansion cohorts of up to 15 patients each are planned, including Hodgkin lymphoma.
cdx-1127
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 Outcomes

Measure
Characterize the adverse events associated with CDX-1127 administration
time frame: Safety follow up is 70 days from last dose.

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Celldex Therapeutics.
Location data was received from the National Cancer Institute and was last updated in April 2016.