Rituximab After Autologous Stem Cell Transplant for Relapsed B-cell Non-Hodgkin's Lymphoma
Study Details
Study Description
Brief Summary
Conventional therapy is effective for diffuse aggressive lymphomas and low grade lymphomas, but is limited by relapse occurs in 40 to 50% of subjects.
This study assesses autologous stem cell transplant (ASCT) supplemented with high-dose therapy increases the event-free survival in diffuse aggressive lymphomas and low grade lymphomas, as an alternative to the limitations of conventional therapy.
Preliminary studies with rituximab in low grade lymphomas indicate a response rate of about 50% with very little toxicity. Rituximab is hypothesized to be a candidate for post-transplant therapy because the majority of malignant lymphomas express the CD20 antigen; rituximab has impressive independent anti-tumor activity; and the antibody has little toxicity outside of the acute administration.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The first 4 subjects received rituximab weekly for 4 weeks at the standard dose of 375 mg/m2, starting 6 weeks after ASCT transplant.
After an observation period to assess acute and late toxicity for the first 4 subjects, subsequent subjects received induction as above followed by an additional 4 week course at 6-months post-ASCT.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rituximab after ASCT Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT. |
Drug: Rituximab 375 mg/m2
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Event-free Survival (EFS) [24 months]
"Events" for EFS were defined as the earlier of post-ASCT relapse or death.
Secondary Outcome Measures
- Overall Survival (OS) [24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
B-cell, CD20+ NHL
-
Evidence of engraftment post-autologous peripheral blood stem cell transplant (PBSC-T), aka autologous stem cell transplant (ASCT)
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
-
Creatinine < 2 mg/dL
-
Bilirubin < 2.0 mg/dL
-
Liver function tests (LFTs) < 5 x upper limit of normal (ULN)
Exclusion Criteria:
-
Graft source from bone marrow
-
Non-responders [progressive disease (PD) or stable disease (SD)] to prior anti-CD20 therapy
-
PD after ASCT
-
Post-ASCT radiotherapy
-
Concomitant treatment with radiotherapy, chemotherapy or immunotherapy including rituximab
-
Evidence of active pneumonitis
-
Evidence of active infection
-
Concurrent prednisone or other systemic steroid medication
-
Nitrosourea therapy within 6 weeks of the first treatment with rituximab
-
Presence of anti-murine antibody (HAMA) reactivity
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University Medical Center | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
Investigators
- Principal Investigator: Sandra J Horning, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- protocol97
- 73750
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rituximab After ASCT |
|---|---|
| Arm/Group Description | Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT |
| Period Title: Overall Study | |
| STARTED | 35 |
| COMPLETED | 29 |
| NOT COMPLETED | 6 |
Baseline Characteristics
| Arm/Group Title | Rituximab After ASCT |
|---|---|
| Arm/Group Description | Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT |
| Overall Participants | 35 |
| Age, Customized (years) [Median (Full Range) ] | |
| aged 16 and older |
51
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
34.3%
|
| Male |
23
65.7%
|
| Lymphoma sub-types (participants) [Number] | |
| Diffuse large B-cell lymphoma (DLCL) |
25
71.4%
|
| Mantle cell lymphoma (MCL) |
3
8.6%
|
| Transformed lymphoma |
3
8.6%
|
| Other B-cell lymphoma |
4
11.4%
|
Outcome Measures
| Title | Event-free Survival (EFS) |
|---|---|
| Description | "Events" for EFS were defined as the earlier of post-ASCT relapse or death. |
| Time Frame | 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab After ASCT |
|---|---|
| Arm/Group Description | Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT |
| Measure Participants | 35 |
| Number (95% Confidence Interval) [percentage of not experiencing EFS event] |
83
|
| Title | Overall Survival (OS) |
|---|---|
| Description | |
| Time Frame | 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab After ASCT |
|---|---|
| Arm/Group Description | Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT |
| Measure Participants | 35 |
| Number (95% Confidence Interval) [percentage of subjects remaining alive] |
88
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Rituximab After ASCT | |
| Arm/Group Description | Rituximab 375 mg/m2 starting 6 weeks after ASCT transplant, and for the 5th and subsequent subjects, a second course at the same dose 6 months after ASCT | |
All Cause Mortality |
||
| Rituximab After ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Rituximab After ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 33/35 (94.3%) | |
| Blood and lymphatic system disorders | ||
| Blood and lymphatic system disorders - Other, neutropenia | 19/35 (54.3%) | 45 |
| Febrile Neutropenia | 1/35 (2.9%) | 1 |
| General disorders | ||
| Death NOS, pneumonitis | 1/35 (2.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumonitis, BCNU-related | 7/35 (20%) | 7 |
| Respiratory, thoracic and mediastinal disorders - Other, Community acquired pneumonia | 4/35 (11.4%) | 4 |
| Pleural effusion | 1/35 (2.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Rituximab After ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/35 (25.7%) | |
| Blood and lymphatic system disorders | ||
| Blood and lymphatic system disorders - Other, neutropenia | 2/35 (5.7%) | 2 |
| Blood and lymphatic system disorders - Other, Thrombocytopenia | 3/35 (8.6%) | 3 |
| Anemia | 4/35 (11.4%) | 4 |
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 | Neal Birkett, MS, RAC |
|---|---|
| Organization | Stanford University Medical Center |
| Phone | 650-723-6456 |
| nbirkett@stanford.edu |
- protocol97
- 73750