Trial Outcomes & Findings for Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer (NCT NCT01022138)
NCT ID: NCT01022138
Last Updated: 2022-12-23
Results Overview
26 evaluable patients will be accrued in this study. A single-arm, single-stage phase II design will be used. If ≥9 out of 26 patients have not progressed by the 4-month follow-up, we will declare that the treatment is effective on TTP.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
At the 4-month follow-up
Results posted on
2022-12-23
Participant Flow
Recruitment Period: 2010-2014; Location: Karmanos Cancer Institute, Detroit, MI
Participant milestones
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
HER2Bi-armed activated T cells Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
Cyclophosphamide After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
Laboratory biomarker analysis The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
|
|---|---|
|
Overall Study
STARTED
|
43
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=43 Participants
HER2Bi-armed activated T cells Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
Cyclophosphamide After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
Laboratory biomarker analysis The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
53.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
43 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At the 4-month follow-upPopulation: There were 32 evaluable HER2 negative patients who received therapy out 42 female patients who were originally enrolled, where one male participant was excluded from the analysis.
26 evaluable patients will be accrued in this study. A single-arm, single-stage phase II design will be used. If ≥9 out of 26 patients have not progressed by the 4-month follow-up, we will declare that the treatment is effective on TTP.
Outcome measures
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=32 Participants
* HER2Bi-armed activated T cells: Immediately after pheresis, lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
* Cyclophosphamide: After recovering from last cycle of chemotherapy (approx. two-four weeks) patients will be restaged. If there is no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
* Laboratory biomarker analysis: Association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
|
|---|---|
|
Number of Participant Who Were Alive Without Progression at 4 Months
|
9 Participants
|
SECONDARY outcome
Timeframe: Followed until death or last observation (assessed up to 5 years), whichever occurs firstOverall survival (OS) was defined as the time duration from the first infusion until death or last observation.
Outcome measures
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=32 Participants
* HER2Bi-armed activated T cells: Immediately after pheresis, lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
* Cyclophosphamide: After recovering from last cycle of chemotherapy (approx. two-four weeks) patients will be restaged. If there is no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
* Laboratory biomarker analysis: Association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
|
|---|---|
|
Overall Survival
|
13.1 Months
Interval 8.6 to 17.4
|
SECONDARY outcome
Timeframe: Following chemotherapy, up to 4 monthsComplete and partial responses; Responses will be evaluated using standard RECIST 1.1 criteria.
Outcome measures
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=32 Participants
* HER2Bi-armed activated T cells: Immediately after pheresis, lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
* Cyclophosphamide: After recovering from last cycle of chemotherapy (approx. two-four weeks) patients will be restaged. If there is no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
* Laboratory biomarker analysis: Association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
|
|---|---|
|
Overall Response Rate
|
9 Participants
|
Adverse Events
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
Serious events: 6 serious events
Other events: 32 other events
Deaths: 27 deaths
Serious adverse events
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=42 participants at risk
HER2Bi-armed activated T cells Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
Cyclophosphamide After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
Laboratory biomarker analysis The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
HER2Bi-armed activated T cells: Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and acti
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|---|---|
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General disorders
Ascites
|
2.4%
1/42 • Number of events 1
|
|
General disorders
AST, SGOT
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Leukocytes
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Cardiac General
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Fever
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Somnolence/depressed level of consciousness
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Hypoxia
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Nausea
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Vomiting
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Musculoskeletal/Soft Tissue
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Creatinine
|
2.4%
1/42 • Number of events 1
|
Other adverse events
| Measure |
HER2Bi-armed Activated T Cells/Cyclophosphamide/Biomarker
n=42 participants at risk
HER2Bi-armed activated T cells Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.
Cyclophosphamide After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide
Laboratory biomarker analysis The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.
HER2Bi-armed activated T cells: Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and acti
|
|---|---|
|
General disorders
Ascites
|
2.4%
1/42 • Number of events 3
|
|
General disorders
Chills
|
71.4%
30/42 • Number of events 82
|
|
General disorders
Creatinine
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Diarrhea
|
4.8%
2/42 • Number of events 2
|
|
General disorders
Dyspnea
|
9.5%
4/42 • Number of events 5
|
|
General disorders
Fatigue
|
73.8%
31/42 • Number of events 92
|
|
General disorders
Fever
|
45.2%
19/42 • Number of events 38
|
|
General disorders
Headache
|
52.4%
22/42 • Number of events 45
|
|
General disorders
Hypertension
|
7.1%
3/42 • Number of events 4
|
|
General disorders
Hypoglycemia
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Hypotension
|
33.3%
14/42 • Number of events 23
|
|
General disorders
Hypoxia
|
4.8%
2/42 • Number of events 2
|
|
General disorders
Metabolic/Laboratory
|
2.4%
1/42 • Number of events 2
|
|
General disorders
Muscle weakness
|
2.4%
1/42 • Number of events 1
|
|
General disorders
Nausea
|
47.6%
20/42 • Number of events 40
|
|
General disorders
Pain
|
9.5%
4/42 • Number of events 5
|
|
General disorders
Somnolence
|
2.4%
1/42 • Number of events 2
|
|
General disorders
Tachycardia
|
4.8%
2/42 • Number of events 2
|
|
General disorders
Vomiting
|
26.2%
11/42 • Number of events 15
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place