- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02227199
Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE)
A Phase I/II Trial of Brentuximab Vedotin (BV), Ifosfamide (I), Carboplatin (C), and Etoposide (E) for Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE)
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine maximally tolerated dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin and etoposide chemotherapy in patients with relapsed or refractory Hodgkin lymphoma.
II. To gain a preliminary assessment of the efficacy of the above regimen.
SECONDARY OBJECTIVES:
I. To determine the safety and toxicity of the above regimen.
II. To determine the ability to proceed to peripheral blood stem cell collection following the above regimen (the impact of above regimen on stem cell reserve).
III. To assess the impact of this regimen on biomarkers from the microenvironment in Hodgkin lymphoma tumors.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) may undergo peripheral blood stem cell (PBSC) mobilization following the 2nd course of study therapy at the discretion of the treating physician.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have primary refractory or first relapse of cluster of differentiation 30 (CD30)+ Hodgkin lymphoma
- Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm; further, at least 1 of these lesions must be positive by positron emission tomography (PET) scan (i.e., Deauville score of 4 or more); Note: CT scans remain the standard for evaluation of nodal disease
- Patients must have a CT of chest, abdomen, and pelvis with PET within 28 days of enrollment; patients with evidence of lymphadenopathy in the neck must have a dedicated CT of neck
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (performance status of 2 will be allowed if poor performance status is thought to be directly secondary to patient's Hodgkin lymphoma [HL])
- Absolute neutrophil count (ANC) >= 1,500/uL, performed within 28 days prior to registration
- Platelets >= 100,000/uL (without transfusion or growth factor support), performed within 28 days prior to registration
- Serum creatinine < 1.5 mg/dl or creatinine clearance (CrCl) > 60 mL/min, performed within 28 days prior to registration
- Total bilirubin < 2 times upper limit of normal (unless due to Gilbert's syndrome), performed within 28 days prior to registration
- Aspartate aminotransferase (AST) < 2.5 times upper limit of normal, performed within 28 days prior to registration
- All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
- Patients must be anticipated to complete 2 cycles of chemotherapy
Exclusion Criteria:
- Patients known to be positive for human immunodeficiency virus (HIV)
- Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol chair or co-chair
- Patients with known allergy, intolerance, or resistance (i.e., remission duration less than 6 months or lack of response) to ifosfamide, carboplatin, or etoposide
- Patients with evidence of active central nervous system lymphoma
- Patients with prior receipt of brentuximab vedotin
- Patients with peripheral neuropathy of > grade 1
- Patients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled arrhythmia); if the patient's cardiac history is questionable, a measurement of left ventricular ejection fraction should be obtained within 42 days prior to registration; patients with left ventricular ejection fraction < 50% are not eligible
- Prior failed (< 5 x 10^6 CD34/kg) peripheral blood stem cell (PBSC) collection
- Patients who had pelvic radiation within 12 months
- Previous chemotherapy/immunotherapy within 3 weeks before study entry
- Concurrent use of other anti-cancer agents or experimental treatments
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3.
Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3.
Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3.
Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
Time Frame: Up to 28 days following the second course of chemotherapy, approximately 70 days
|
Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity.
Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
|
Up to 28 days following the second course of chemotherapy, approximately 70 days
|
Percentage of Patients That Achieve a Complete Remission Following Study Treatment
Time Frame: 3 weeks following the completion of chemotherapy
|
3 weeks following the completion of chemotherapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
2 Year Overall Survival
Time Frame: Up to 2 years from initiation of study therapy.
|
Up to 2 years from initiation of study therapy.
|
2 Year Progression-free Survival
Time Frame: Up to 2 years from initiation of therapy.
|
Up to 2 years from initiation of therapy.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Hodgkin Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Keratolytic Agents
- Immunotoxins
- Carboplatin
- Etoposide
- Etoposide phosphate
- Antibodies
- Ifosfamide
- Isophosphamide mustard
- Podophyllotoxin
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Brentuximab Vedotin
- Immunoconjugates
Other Study ID Numbers
- 9111 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2014-01782 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RG1714038 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Hodgkin Lymphoma
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
University of WashingtonRecruitingRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin LymphomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Recurrent Adult Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Follicular Lymphoma | Recurrent Lymphoplasmacytic Lymphoma | AIDS-Related Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)RecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous... and other conditionsUnited States
-
Northwestern UniversityNational Cancer Institute (NCI); Merck Sharp & Dohme LLCActive, not recruitingLymphocyte-Rich Classical Hodgkin Lymphoma | Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma | Recurrent Mixed Cellularity Classical Hodgkin Lymphoma | Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma | Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma | Refractory Mixed... and other conditionsUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)RecruitingDiffuse Large B-Cell Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Recurrent Waldenstrom... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)WithdrawnHIV Infection | Recurrent Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | AIDS-Related Non-Hodgkin Lymphoma | AIDS-Related Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Hodgkin Lymphoma | Refractory Childhood Hodgkin Lymphoma | Recurrent Childhood Hodgkin LymphomaUnited States, Canada
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRefractory Hodgkin Lymphoma | Recurrent Adult Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Prolymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | T-Cell Chronic Lymphocytic Leukemia | Recurrent Childhood Non-Hodgkin... and other conditionsUnited States, Germany
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States