BV-ICE: Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This phase I/II trial studies the side effects and best dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide chemotherapy regimen may kill more cancer cells.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
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.
-
To gain a preliminary assessment of the efficacy of the above regimen.
SECONDARY OBJECTIVES:
-
To determine the safety and toxicity of the above regimen.
-
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).
-
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 Design
Arms and Interventions
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. |
Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Carboplatin
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Ifosfamide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
|
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. |
Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Carboplatin
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Ifosfamide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
|
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. |
Drug: Brentuximab Vedotin
Given IV
Other Names:
Drug: Carboplatin
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Ifosfamide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy [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.
- Percentage of Patients That Achieve a Complete Remission Following Study Treatment [3 weeks following the completion of chemotherapy]
Secondary Outcome Measures
- 2 Year Overall Survival [Up to 2 years from initiation of study therapy.]
- 2 Year Progression-free Survival [Up to 2 years from initiation of therapy.]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- University of Washington
- National Cancer Institute (NCI)
- Seagen Inc.
Investigators
- Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium
Study Documents (Full-Text)
More Information
Publications
None provided.- 9111
- NCI-2014-01782
- 9111
- P30CA015704
- RG1714038
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 2: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) |
---|---|---|---|
Arm/Group Description | Patients receive brentuximab Vedotin 1.2mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab Vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab Vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies |
Period Title: Overall Study | |||
STARTED | 3 | 3 | 39 |
COMPLETED | 3 | 3 | 35 |
NOT COMPLETED | 0 | 0 | 4 |
Baseline Characteristics
Arm/Group Title | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Total |
---|---|---|---|---|
Arm/Group Description | 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. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | 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. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | 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. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Total of all reporting groups |
Overall Participants | 3 | 3 | 39 | 45 |
Age (Count of Participants) | ||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
3
100%
|
3
100%
|
39
100%
|
45
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | ||||
Female |
2
66.7%
|
0
0%
|
27
69.2%
|
29
64.4%
|
Male |
1
33.3%
|
3
100%
|
12
30.8%
|
16
35.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
0
0%
|
0
0%
|
4
10.3%
|
4
8.9%
|
Not Hispanic or Latino |
3
100%
|
3
100%
|
35
89.7%
|
41
91.1%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
4
10.3%
|
4
8.9%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
2
5.1%
|
2
4.4%
|
White |
3
100%
|
3
100%
|
32
82.1%
|
38
84.4%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
1
2.6%
|
1
2.2%
|
Region of Enrollment (participants) [Number] | ||||
United States |
3
100%
|
3
100%
|
39
100%
|
45
100%
|
Outcome Measures
Title | Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy |
---|---|
Description | 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. |
Time Frame | Up to 28 days following the second course of chemotherapy, approximately 70 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment (Brentuximab, Ifosfamide, Carboplatin, Etoposide) |
---|---|
Arm/Group Description | Patients receive brentuximab vedotin 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies |
Measure Participants | 6 |
Number [mg/kg] |
1.5
|
Title | Percentage of Patients That Achieve a Complete Remission Following Study Treatment |
---|---|
Description | |
Time Frame | 3 weeks following the completion of chemotherapy |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) |
---|---|---|---|
Arm/Group Description | Patients receive brentuximab Vedotin 1.2mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab Vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab Vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies |
Measure Participants | 3 | 3 | 39 |
Count of Participants [Participants] |
3
100%
|
3
100%
|
26
66.7%
|
Title | 2 Year Overall Survival |
---|---|
Description | |
Time Frame | Up to 2 years from initiation of study therapy. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) |
---|---|---|---|
Arm/Group Description | Patients receive brentuximab vedotin 1.2mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies |
Measure Participants | 3 | 3 | 39 |
Count of Participants [Participants] |
3
100%
|
3
100%
|
37
94.9%
|
Title | 2 Year Progression-free Survival |
---|---|
Description | |
Time Frame | Up to 2 years from initiation of therapy. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) |
---|---|---|---|
Arm/Group Description | Patients receive brentuximab vedotin 1.2mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies |
Measure Participants | 3 | 3 | 39 |
Count of Participants [Participants] |
2
66.7%
|
3
100%
|
33
84.6%
|
Adverse Events
Time Frame | Adverse events were collected starting after the first dose of study treatment and collected through 30 days after the last dose of study drug, or until the patient receives an alternative anti-cancer therapy, whichever date comes first, approximately 60 days. | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | |||
Arm/Group Description | Patients receive brentuximab vedotin 1.2mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies | Patients receive brentuximab vedotin 1.5mg/kg 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 HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. | |||
All Cause Mortality |
||||||
Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/3 (0%) | 0/3 (0%) | 2/39 (5.1%) | |||
Serious Adverse Events |
||||||
Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/3 (0%) | 1/3 (33.3%) | 11/39 (28.2%) | |||
Cardiac disorders | ||||||
Tachycardia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
Endocrine disorders | ||||||
Diabetic Ketoacidosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/39 (5.1%) | 2 |
Gastrointestinal disorders | ||||||
Gastroenteritis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
General disorders | ||||||
Fever | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/39 (7.7%) | 3 |
Neutropenic Fever | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Infections and infestations | ||||||
Septic Shock | /3 (NaN) | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 | |
Sepsis | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 4/39 (10.3%) | 4 |
Investigations | ||||||
Elevated Lactate | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/39 (5.1%) | 2 |
Metabolism and nutrition disorders | ||||||
Hypokalemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
Hyperglycemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
Skin and subcutaneous tissue disorders | ||||||
Sweet Syndrome | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
Erythematous Rash | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/39 (2.6%) | 1 |
Vascular disorders | ||||||
Hypotension | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/39 (5.1%) | 2 |
Pulmonary Embolism | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/39 (2.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/3 (100%) | 3/3 (100%) | 39/39 (100%) | |||
Blood and lymphatic system disorders | ||||||
Anemia | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 8/39 (20.5%) | 10 |
Leukocytosis | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 4/39 (10.3%) | 4 |
Cardiac disorders | ||||||
Tachycardia | 2/3 (66.7%) | 2 | 2/3 (66.7%) | 2 | 11/39 (28.2%) | 11 |
Palpitations | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Hypotension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/39 (10.3%) | 4 |
Eye disorders | ||||||
Blurred Vision | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/39 (5.1%) | 2 |
Gastrointestinal disorders | ||||||
Abdominal Pain | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 11/39 (28.2%) | 13 |
Constipation | 2/3 (66.7%) | 2 | 3/3 (100%) | 4 | 18/39 (46.2%) | 19 |
Diarrhea | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 10/39 (25.6%) | 15 |
Vomiting | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 18/39 (46.2%) | 23 |
Nausea | 2/3 (66.7%) | 3 | 3/3 (100%) | 3 | 29/39 (74.4%) | 40 |
Dry Mouth | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 2/39 (5.1%) | 2 |
Gastroesophageal Reflux Disease | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 12/39 (30.8%) | 12 |
Mucositis Oral | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 2/39 (5.1%) | 2 |
General disorders | ||||||
Non-cardiac chest pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 6/39 (15.4%) | 7 |
Infusion related reaction | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/39 (5.1%) | 2 |
Fatigue | 2/3 (66.7%) | 4 | 3/3 (100%) | 3 | 16/39 (41%) | 19 |
Fever | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 4/39 (10.3%) | 6 |
Hiccups | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Night Sweats | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/39 (12.8%) | 5 |
Pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 7/39 (17.9%) | 8 |
Edema Limbs | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Pain at Hickman Site | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 4/39 (10.3%) | 4 |
Flushing | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Infections and infestations | ||||||
Upper Respiratory Infection | 0/3 (0%) | 0 | 2/3 (66.7%) | 4 | 6/39 (15.4%) | 6 |
Investigations | ||||||
Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 12/39 (30.8%) | 30 |
Aspartate aminotransferase increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 10/39 (25.6%) | 17 |
Platelet Count Decreased | 2/3 (66.7%) | 3 | 1/3 (33.3%) | 3 | 5/39 (12.8%) | 8 |
Weight Loss | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/39 (7.7%) | 3 |
Neutrophil Count Decreased | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 1/39 (2.6%) | 1 |
Metabolism and nutrition disorders | ||||||
Anorexia | 2/3 (66.7%) | 2 | 3/3 (100%) | 3 | 6/39 (15.4%) | 7 |
Hypokalemia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 12/39 (30.8%) | 13 |
Hypomagnesemia | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 6/39 (15.4%) | 7 |
Hyperglycemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/39 (10.3%) | 4 |
Hypophosphatemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/39 (12.8%) | 6 |
Hypocalcemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/39 (5.1%) | 3 |
Musculoskeletal and connective tissue disorders | ||||||
Back Pain | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 6/39 (15.4%) | 6 |
Bone Pain | 0/3 (0%) | 0 | 3/3 (100%) | 3 | 6/39 (15.4%) | 7 |
Myalgia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 2/39 (5.1%) | 2 |
Pain in Extremity | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/39 (12.8%) | 5 |
Arthralgia | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 3/39 (7.7%) | 5 |
Nervous system disorders | ||||||
Headache | 3/3 (100%) | 5 | 1/3 (33.3%) | 1 | 15/39 (38.5%) | 18 |
Dizziness | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 4/39 (10.3%) | 5 |
Peripheral Sensory Neuropathy | 2/3 (66.7%) | 3 | 1/3 (33.3%) | 1 | 10/39 (25.6%) | 12 |
Psychiatric disorders | ||||||
Anxiety | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 5/39 (12.8%) | 5 |
Insomnia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 4/39 (10.3%) | 4 |
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 6/39 (15.4%) | 6 |
Dyspnea | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 2/39 (5.1%) | 2 |
Allergic Rhinitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 7/39 (17.9%) | 7 |
Skin and subcutaneous tissue disorders | ||||||
Alopecia | 3/3 (100%) | 3 | 1/3 (33.3%) | 1 | 19/39 (48.7%) | 19 |
Rash maculo-papular | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 8/39 (20.5%) | 8 |
Pruritus | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 7/39 (17.9%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Ajay Gopal |
---|---|
Organization | University of Washington |
Phone | 26-606-2037 |
agopal@uw.edu |
- 9111
- NCI-2014-01782
- 9111
- P30CA015704
- RG1714038