SGN-30 and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This randomized phase II trial studies the side effects and how well giving monoclonal antibody SGN-30 together with combination chemotherapy works in treating patients with Hodgkin lymphoma that has returned after a period of improvement or did not respond to previous treatment. Monoclonal antibodies, such as SGN-30, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine hydrochloride, vinorelbine tartrate, and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody SGN-30 together with combination chemotherapy may kill more cancer cells and shrink tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To determine the complete and partial response rates following treatment with the anti-cluster of differentiation (CD) 30 antibody, SGN-30 (monoclonal antibody SGN-30), and gemcitabine (gemcitabine hydrochloride), vinorelbine (vinorelbine tartrate), and pegylated liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) (GVD) in patients with relapsed or refractory Hodgkin lymphoma (HL).
-
To assess time to progression and overall survival in patients treated with SGN-30 and GVD in patients with relapsed or refractory Hodgkin lymphoma (HL).
-
To evaluate the toxicity of SGN-30 in combination with GVD in patients with relapsed and refractory HL.
SECONDARY OBJECTIVES:
-
To determine the pharmacokinetic profile of SGN-30 when combined with GVD chemotherapy.
-
To correlate soluble (s) CD30 levels with response to treatment. III. To determine the incidence of human anti-chimeric antibodies (HACA) formation following repetitive SGN-30 dosing.
-
To correlate Fc gamma receptor polymorphisms with response to treatment.
OUTLINE:
Part 1 (closed to accrual as of 5/18/2007): Patients receive monoclonal antibody SGN-30 intravenously (IV) over 2 hours, vinorelbine tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride liposome IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days until 10 out of 16 patients complete 1 course in the absence of unacceptable toxicity. Subsequent patients receive treatment on part 2.
Part 2: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive monoclonal antibody SGN-30 IV over 2 hours, vinorelbine tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride liposome IV over 90 minutes on days 1 and 8.
Arm II (closed to accrual as of 12/4/07): Patients receive placebo IV over 2 hours, vinorelbine tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride liposome IV over 90 minutes on days 1 and 8.
Treatment in both arms repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: Treatment with SGN-30/placebo was stopped on 4/12/2007 due to pulmonary toxicity.
After completion of study treatment, patients are followed up periodically for up to 10 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (SGN-30, chemotherapy) Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. |
Biological: monoclonal antibody SGN-30
Given IV
Other Names:
Drug: vinorelbine tartrate
Given IV
Other Names:
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
|
| Active Comparator: Arm II (placebo, chemotherapy) Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. |
Other: placebo
Given IV
Other Names:
Drug: vinorelbine tartrate
Given IV
Other Names:
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Overall Response (OR) [Up to 10 years]
The number of participants who respond (complete or partial) to treatment. Response was defined using the revised criteria for malignant lymphoma. Complete response (CR): complete disappearance of all detectable disease; partial response (PR): >= 50% reduction in sum of the product of diameters of indicator lesions.
Secondary Outcome Measures
- Event Free Survival (EFS) [Up to 10 years]
Event free survival is the time from trial entry until progression, death, or termination of treatment due to nonresponse. Patients who went on to receive a stem cell transplant (SCT) were not censored from the EFS survival at the time of transplant and were only considered failures at the time of relapse or death from any cause. The median EFS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.
- Overall Survival (OS) At 1 Year [1 year]
Percentage of patients who were alive at 1 year. The 1-year survival rate was estimated using the Kaplan Meier method.
Other Outcome Measures
- Peak Serum Level of Monoclonal Antibody SGN-30 [Up to day 21 of course 6]
Record the highest serum level of monoclonal antibody SGN-30 achieved.
- sCD30 Levels [Up to day 21 of course 6]
A 2-sided t-test with alpha = 0.05 will be used to compare sCD30 levels between responders (OR) and non-responders groups.
- Fc Gamma Receptor Polymorphisms [Baseline]
Fisher's exact test with 2-sided alpha = 0.05 will be used to compare the response probabilities in patients with V/V (valine expression), V/F (heterozygous), and F/F (homozygous for phenylalanine) for each of Fc gamma RIIIa a
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically documented CD30-positive classical Hodgkin lymphoma according to the World Health Organization (WHO) classification of lymphoid malignancies that is recurrent or refractory after at least one prior therapy
-
Note: Patients with nodular lymphocyte predominant HL are not eligible; all other subtypes including nodular sclerosis, lymphocyte-depleted, lymphocyte rich, and mixed cellularity HL may be enrolled
-
Core needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable; if the original diagnostic specimen is not available, specimens obtained at relapse may be submitted; if multiple specimens are available, please submit the most recent; failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
-
Patients must have relapsed or refractory disease after at least one prior therapy, with at least a 3 week interval from the completion of the most recent chemotherapy or radiotherapy regimen; recovery to =< grade 1 from all toxicities related to the prior treatments is required; patients who have previously received a stem cell transplant are permitted to enroll on this study
-
Prior treatment with an anti-CD30 antibody, gemcitabine, vinorelbine, or pegylated liposomal doxorubicin is not permitted
-
No uncontrolled angina, no myocardial infarction (MI) within 6 months of study entry, and no New York Heart Association (NYHA) class II or greater congestive heart failure (CHF)
-
Baseline left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) must be >= 45%
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-
Measurable disease must be present on either physical examination or imaging studies; evaluable or non-measurable disease alone is not acceptable
-
Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm
-
Non-measurable disease includes all other lesions, including small lesions (< 10 mm) and truly non-measurable lesions
-
Lesions that are considered non-measurable include the following:
-
Bone lesions (lesions, if present, should be noted)
-
Bone marrow involvement (if present, this should be noted)
-
Ascites
-
Pleural/pericardial effusion
-
Lymphangitis cutis/pulmonis
-
Pregnant or nursing women may not be enrolled; women of childbearing potential must have a negative serum or urine pregnancy test prior to registration; women and men of reproductive potential should agree to use an effective means of birth control
-
Corrected diffusion capacity of carbon monoxide (DLCO) >= 50%
-
Absolute neutrophil count (ANC) >= 1,200/uL
-
Platelet count >= 100,000/uL
-
Creatinine =< 2.0 mg/dL
-
Bilirubin =< 2.0 mg/dL
-
Absent a history of Gilbert's disease
-
Aspartate aminotransferase (AST) =< 2.0 x upper limits of normal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer and Leukemia Group B | Chicago | Illinois | United States | 60606 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Kristie Blum, Cancer and Leukemia Group B
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02822
- NCI-2012-02822
- CALGB-50502
- CALGB-50502
- U10CA031946
- P30CA014236
Study Results
Participant Flow
| Recruitment Details | From April 2006 to December 2007 10 institutions recruited 30 participants to this trial. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Period Title: Overall Study | ||
| STARTED | 23 | 7 |
| COMPLETED | 11 | 3 |
| NOT COMPLETED | 12 | 4 |
Baseline Characteristics
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) | Total |
|---|---|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Total of all reporting groups |
| Overall Participants | 23 | 7 | 30 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
35
|
38
|
35
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
5
21.7%
|
2
28.6%
|
7
23.3%
|
| Male |
18
78.3%
|
5
71.4%
|
23
76.7%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
8.7%
|
0
0%
|
2
6.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
13%
|
1
14.3%
|
4
13.3%
|
| White |
18
78.3%
|
6
85.7%
|
24
80%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
23
100%
|
7
100%
|
30
100%
|
| Prior autologous transplant (participants) [Number] | |||
| Yes |
8
34.8%
|
3
42.9%
|
11
36.7%
|
| No |
15
65.2%
|
4
57.1%
|
19
63.3%
|
Outcome Measures
| Title | Number of Participants With Overall Response (OR) |
|---|---|
| Description | The number of participants who respond (complete or partial) to treatment. Response was defined using the revised criteria for malignant lymphoma. Complete response (CR): complete disappearance of all detectable disease; partial response (PR): >= 50% reduction in sum of the product of diameters of indicator lesions. |
| Time Frame | Up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Measure Participants | 23 | 7 |
| Number [participants] |
15
65.2%
|
4
57.1%
|
| Title | Event Free Survival (EFS) |
|---|---|
| Description | Event free survival is the time from trial entry until progression, death, or termination of treatment due to nonresponse. Patients who went on to receive a stem cell transplant (SCT) were not censored from the EFS survival at the time of transplant and were only considered failures at the time of relapse or death from any cause. The median EFS with 95% confidence interval (CI) was estimated using the Kaplan Meier method. |
| Time Frame | Up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Measure Participants | 23 | 7 |
| Median (95% Confidence Interval) [months] |
11.3
|
4.1
|
| Title | Overall Survival (OS) At 1 Year |
|---|---|
| Description | Percentage of patients who were alive at 1 year. The 1-year survival rate was estimated using the Kaplan Meier method. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Measure Participants | 23 | 7 |
| Median (95% Confidence Interval) [percentage of participants] |
86
373.9%
|
30
428.6%
|
| Title | Peak Serum Level of Monoclonal Antibody SGN-30 |
|---|---|
| Description | Record the highest serum level of monoclonal antibody SGN-30 achieved. |
| Time Frame | Up to day 21 of course 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was only available on 10 participants from Arm 1. (No participants from Arm II were evaluable for this endpoint as they did not receive SGN-30 per protocol.) |
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) |
|---|---|
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Measure Participants | 10 |
| Median (Full Range) [mg/ml] |
339
|
| Title | sCD30 Levels |
|---|---|
| Description | A 2-sided t-test with alpha = 0.05 will be used to compare sCD30 levels between responders (OR) and non-responders groups. |
| Time Frame | Up to day 21 of course 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Nine participants submitted pretreatment sCD30 samples. |
| Arm/Group Title | Responders | Non-responders |
|---|---|---|
| Arm/Group Description | Subset of patients who achieved an overall response, as describer in primary outcome measure 1. | Subset of patients who did not achieve an overall response, as defined in primary outcome measure 1 |
| Measure Participants | 4 | 5 |
| Median (Full Range) [U/ml] |
174.2
|
76.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm I (SGN-30, Chemotherapy), Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.06 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Fc Gamma Receptor Polymorphisms |
|---|---|
| Description | Fisher's exact test with 2-sided alpha = 0.05 will be used to compare the response probabilities in patients with V/V (valine expression), V/F (heterozygous), and F/F (homozygous for phenylalanine) for each of Fc gamma RIIIa a |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Fc gamma receptor polymorphisms were assessed in 28 participants. |
| Arm/Group Title | Responders | Non-responders |
|---|---|---|
| Arm/Group Description | Subset of patients who achieved an overall response, as describer in primary outcome measure 1. | Subset of patients who did not achieve an overall response, as defined in primary outcome measure 1 |
| Measure Participants | 17 | 11 |
| V/V |
0
0%
|
0
0%
|
| F/F |
10
43.5%
|
6
85.7%
|
| F/V |
7
30.4%
|
5
71.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm I (SGN-30, Chemotherapy), Arm II (Placebo, Chemotherapy) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) | ||
| Arm/Group Description | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. monoclonal antibody SGN-30: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days. No prior stem cell transplant: SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8. Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8. placebo: Given IV vinorelbine tartrate: Given IV pegylated liposomal doxorubicin hydrochloride: Given IV gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies pharma | ||
All Cause Mortality |
||||
| Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/23 (39.1%) | 1/7 (14.3%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Hemoglobin decreased | 6/23 (26.1%) | 6 | 1/7 (14.3%) | 1 |
| Cardiac disorders | ||||
| Sinus tachycardia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Supraventricular tachycardia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Constipation | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Diarrhea | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Dry mouth | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Dysphagia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Ear, nose and throat examination abnormal | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Gastritis | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Ileus | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Mucositis oral | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Nausea | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Stomach pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Vomiting | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| General disorders | ||||
| Chest pain | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Chills | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Edema limbs | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Fatigue | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Fever | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Visceral edema | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Infections and infestations | ||||
| Infection | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Pneumonia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Sepsis | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Upper respiratory infection | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Alanine aminotransferase increased | 4/23 (17.4%) | 4 | 1/7 (14.3%) | 1 |
| Alkaline phosphatase increased | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Aspartate aminotransferase increased | 6/23 (26.1%) | 6 | 0/7 (0%) | 0 |
| Blood bilirubin increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Creatinine increased | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| INR increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Laboratory test abnormal | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Leukocyte count decreased | 4/23 (17.4%) | 4 | 1/7 (14.3%) | 1 |
| Lymphocyte count decreased | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Neutrophil count decreased | 5/23 (21.7%) | 5 | 1/7 (14.3%) | 1 |
| Platelet count decreased | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Blood glucose increased | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Serum albumin decreased | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Serum calcium decreased | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Serum glucose decreased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Serum magnesium decreased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Serum magnesium increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Serum phosphate decreased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Serum potassium decreased | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Serum sodium decreased | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Pain in extremity | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||
| Dysgeusia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Headache | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Peripheral sensory neuropathy | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Psychiatric disorders | ||||
| Anxiety | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Depression | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Insomnia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chylothorax | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Cough | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Dyspnea | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Hypoxia | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Pleural effusion | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Pneumonitis | 4/23 (17.4%) | 4 | 0/7 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Body odor | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Hand-and-foot syndrome | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Photosensitivity | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Urticaria | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Arm I (SGN-30, Chemotherapy) | Arm II (Placebo, Chemotherapy) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/23 (91.3%) | 7/7 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 2/23 (8.7%) | 2 | 1/7 (14.3%) | 1 |
| Hemoglobin decreased | 15/23 (65.2%) | 31 | 5/7 (71.4%) | 8 |
| Hemolysis | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||
| Cardiac pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Edema | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Palpitations | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Ear pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Eye disorders | ||||
| Vision blurred | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Constipation | 5/23 (21.7%) | 6 | 1/7 (14.3%) | 1 |
| Diarrhea | 1/23 (4.3%) | 1 | 2/7 (28.6%) | 3 |
| Dry mouth | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Ear, nose and throat examination abnormal | 4/23 (17.4%) | 5 | 0/7 (0%) | 0 |
| Ileus | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Mucositis oral | 5/23 (21.7%) | 5 | 0/7 (0%) | 0 |
| Nausea | 11/23 (47.8%) | 16 | 4/7 (57.1%) | 5 |
| Stomach pain | 0/23 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vomiting | 2/23 (8.7%) | 2 | 2/7 (28.6%) | 2 |
| General disorders | ||||
| Chest pain | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Chills | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Edema limbs | 3/23 (13%) | 6 | 2/7 (28.6%) | 2 |
| Fatigue | 8/23 (34.8%) | 13 | 6/7 (85.7%) | 6 |
| Fever | 5/23 (21.7%) | 6 | 0/7 (0%) | 0 |
| Joint- Late RT Morbidity Scoring | 1/23 (4.3%) | 2 | 0/7 (0%) | 0 |
| Localized edema | 0/23 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pain | 2/23 (8.7%) | 3 | 0/7 (0%) | 0 |
| Visceral edema | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Immune system disorders | ||||
| Hypersensitivity | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Infections and infestations | ||||
| Catheter related infection | 1/23 (4.3%) | 2 | 0/7 (0%) | 0 |
| Pneumonia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Skin infection | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Upper aerodigestive tract infection | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Upper respiratory infection | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Vascular access complication | 1/23 (4.3%) | 4 | 0/7 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 9/23 (39.1%) | 12 | 4/7 (57.1%) | 6 |
| Alkaline phosphatase increased | 4/23 (17.4%) | 6 | 0/7 (0%) | 0 |
| Aspartate aminotransferase increased | 8/23 (34.8%) | 12 | 3/7 (42.9%) | 5 |
| Coagulopathy | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Creatinine increased | 1/23 (4.3%) | 1 | 1/7 (14.3%) | 1 |
| INR increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Leukocyte count decreased | 10/23 (43.5%) | 15 | 4/7 (57.1%) | 7 |
| Lymphocyte count decreased | 7/23 (30.4%) | 11 | 2/7 (28.6%) | 4 |
| Neutrophil count decreased | 16/23 (69.6%) | 21 | 6/7 (85.7%) | 8 |
| Platelet count decreased | 16/23 (69.6%) | 32 | 3/7 (42.9%) | 7 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 3/23 (13%) | 3 | 2/7 (28.6%) | 2 |
| Blood glucose increased | 3/23 (13%) | 5 | 2/7 (28.6%) | 2 |
| Serum albumin decreased | 5/23 (21.7%) | 9 | 1/7 (14.3%) | 1 |
| Serum calcium decreased | 4/23 (17.4%) | 4 | 1/7 (14.3%) | 1 |
| Serum magnesium decreased | 0/23 (0%) | 0 | 1/7 (14.3%) | 1 |
| Serum potassium decreased | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Serum potassium increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Serum sodium decreased | 3/23 (13%) | 4 | 1/7 (14.3%) | 1 |
| Serum sodium increased | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/23 (13%) | 5 | 1/7 (14.3%) | 1 |
| Back pain | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Bone pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Chest wall pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Joint disorder | 1/23 (4.3%) | 2 | 0/7 (0%) | 0 |
| Muscle weakness | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Myalgia | 2/23 (8.7%) | 3 | 0/7 (0%) | 0 |
| Neck pain | 1/23 (4.3%) | 1 | 1/7 (14.3%) | 1 |
| Pain in extremity | 2/23 (8.7%) | 3 | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||||
| Dizziness | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Headache | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Peripheral motor neuropathy | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Peripheral sensory neuropathy | 4/23 (17.4%) | 5 | 0/7 (0%) | 0 |
| Tremor | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Depression | 2/23 (8.7%) | 2 | 0/7 (0%) | 0 |
| Insomnia | 3/23 (13%) | 3 | 0/7 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Pelvic pain | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 0/23 (0%) | 0 | 1/7 (14.3%) | 1 |
| Aspiration | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Cough | 3/23 (13%) | 3 | 1/7 (14.3%) | 1 |
| Dyspnea | 6/23 (26.1%) | 8 | 2/7 (28.6%) | 2 |
| Epistaxis | 0/23 (0%) | 0 | 1/7 (14.3%) | 2 |
| Hypoxia | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Laryngeal mucositis | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Pneumonitis | 0/23 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Hand-and-foot syndrome | 8/23 (34.8%) | 16 | 2/7 (28.6%) | 3 |
| Pruritus | 2/23 (8.7%) | 4 | 0/7 (0%) | 0 |
| Rash desquamating | 3/23 (13%) | 3 | 1/7 (14.3%) | 2 |
| Skin disorder | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Sweating | 2/23 (8.7%) | 6 | 1/7 (14.3%) | 1 |
| Urticaria | 1/23 (4.3%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension | 1/23 (4.3%) | 2 | 0/7 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Dr. Kristie Blum |
|---|---|
| Organization | The Ohio State University |
| Phone | |
| kristie.blum@osumc.edu |
- NCI-2012-02822
- NCI-2012-02822
- CALGB-50502
- CALGB-50502
- U10CA031946
- P30CA014236