Rituxan+BEAM: Rituxan + BEAM and Auto Stem Cell Transplant for High Risk Lymphoma or Hodgkin's Disease
Study Details
Study Description
Brief Summary
High-dose chemotherapy followed by autologous (the patient's own) peripheral blood (circulating blood) stem cell (cells that divide to form white cells, red cells and cells that help clot) transplantation is a conventional treatment for patients with lymphoma (cancer of lymph glands) and Hodgkin's disease (cancer of lymph glands) after first relapse (recurrence of disease). For patients who did not have a complete response after traditional chemotherapy, the chance is high that the tumor will return even after high-dose chemotherapy. To improve the response and decrease the chance of relapse, doctors have used rituximab, an antibody that kills lymphoma cells, both before and after transplantation. These doctors have reported that more patients had control of the tumor for an extended period of time using rituximab with high-dose chemotherapy with autologous stem cell transplantation. How widely this is applicable is not known.
The purpose of this clinical research trial is to confirm that there is a good control of tumor in patients with lymphoma or Hodgkin's disease treated with rituximab and conventional stem cell transplantation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Subjects will receive the chemotherapy through a plastic tube (catheter) placed into a vein under the collarbone. The antibody rituximab is given on the day of admission. The subject will also start a six-day course of chemotherapy at that time. The chemotherapy will consist of the following drugs: BCNU, etoposide also called VP-16, Ara-C also called cytosine arabinoside, and melphalan. BCNU is given on the first day, Ara-C and VP-16 on the second, third, fourth and fifth days, and melphalan on the sixth day. The infusion of blood stem cells is given through the catheter the day after the last dose of chemotherapy. This is called Day 0. A week later the subject will receive shots under the skin of Neupogen to help the stem cells grow quickly. Three additional doses of rituximab are given weekly starting 2 weeks later. If the subject recovers and is discharged from the hospital before getting all the doses of rituximab, they can receive the remainder in clinic.
Patients will remain in the hospital for approximately 3-4 weeks, and in the Houston area for about 30 days from the infusion of the donor cells. The patient will have blood, urine, bone marrow, and x-ray examinations performed as necessary to monitor the results of treatment. They will have blood tests daily while hospitalized.
As an outpatient, the patient will be monitored to make sure their immune system (system in the body that helps protect the body and fights bacterial, viral and fungal infections) is recovering, and the patient may require additional infusions of immunoglobulins (infection-fighting blood proteins) until the blood protein levels are safe. The patient will also be taking antibiotic pills for about 6 months to prevent infections. They will have x-rays and other diagnostic tests (PET scans) every 6-12 months during the next 5 years to make sure the tumor stays under control.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: BEAM+R: Autologous Stem Cell Transplant Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells |
Drug: Melphalan
Given on Day -1
Melphalan is administered according to the current SOP.
Other Names:
Drug: Ara-C
200 mg/m2 IB BID given on Days -5, -4, -3, -2
Other Names:
Drug: VP-16
200 mg/m2 IV BID given on Days -5, -4, -3, -2
Other Names:
Drug: BCNU
BCNU 300 mg/m2 IV given on Day -6
Other Names:
Drug: Rituxan
375 mg/m2 IB given on Days -6, +14, +21, +28
Other Names:
Drug: Stem Cells
Stem cells given on Day 0
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Disease-free Survival [12 months post-transplant]
Disease-free survival at 12 months post-transplant in patients with Hodgkin's disease or non-Hodgkin's lymphomas
Secondary Outcome Measures
- Median Days to Neutrophil Engraftment [30 days post-transplant]
Neutrophil engraftment was recorded as the first day that absolute neutrophil counts (ANC) exceeds 0.5 X 10^9/L for three consecutive readings.
- Number of Participants With Overall Best Response Achieved After Transplantation [3 months post-transplant]
Response was summarized as complete remission (CR): disappearance of all evidence of disease; partial remission (PR): regression of measurable disease (>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses) and no new sites; stable disease (SD): failure to attain CR/PR/PD; relapsed disease or progressive disease (PD): any new lesion or increase by >= 50% of previously involved sites from nadir.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with biopsy-proven, relapsed, or refractory CD20+ lymphoma, or HD.
-
At least 2e6 CD34+/kg autologous PBSC stored. If patients are non-mobilizers, then at least 2e8 TNC/kg autologous marrow should be stored.
-
Patient is not pregnant.
-
Zubrod performance status less than or equal to 2.
-
Life expectancy is not severely limited by concomitant illness.
-
Left ventricular ejection fraction greater than or equal to 50%.
-
No uncontrolled arrhythmias or symptomatic cardiac disease.
-
FEV1, FVC and DLCO greater than or equal to 50%.
-
No symptomatic pulmonary disease.
-
Serum creatinine less than or equal to 1.5 mg/dL.
-
Serum bilirubin less than or equal to 2X upper limit of normal, SGPT less than or equal to 3X upper limit of normal.
-
No evidence of chronic active hepatitis or cirrhosis.
-
No effusion or ascites greater than or equal to 1L prior to drainage.
-
HIV negative.
-
Patient or guardian able to sign informed consent.
-
Patients of any age may be enrolled on this protocol.
Exclusion Criteria:
- Anyone not meeting the above criteria.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
| 2 | The Methodist Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor College of Medicine
- The Methodist Hospital Research Institute
- Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
- Principal Investigator: George Carrum, MD, Associate Professor; Director-Adult Outpatient Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-11892
- Rituxan+BEAM
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rituxan+BEAM: Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 |
| Period Title: Overall Study | |
| STARTED | 75 |
| COMPLETED | 28 |
| NOT COMPLETED | 47 |
Baseline Characteristics
| Arm/Group Title | Rituxan+BEAM: Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 |
| Overall Participants | 75 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
53
|
| Sex: Female, Male (Count of Participants) | |
| Female |
32
42.7%
|
| Male |
43
57.3%
|
| Disease at diagnosis (participants) [Number] | |
| Hodgkin's Disease |
25
33.3%
|
| Non-Hodgkin's Lymphoma |
50
66.7%
|
Outcome Measures
| Title | Disease-free Survival |
|---|---|
| Description | Disease-free survival at 12 months post-transplant in patients with Hodgkin's disease or non-Hodgkin's lymphomas |
| Time Frame | 12 months post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | BEAM + R: Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 |
| Measure Participants | 75 |
| All patients |
76
|
| Hodgkin's Disease |
88
|
| Non-Hodgkin's Lymphomas |
70
|
| Title | Median Days to Neutrophil Engraftment |
|---|---|
| Description | Neutrophil engraftment was recorded as the first day that absolute neutrophil counts (ANC) exceeds 0.5 X 10^9/L for three consecutive readings. |
| Time Frame | 30 days post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| All of the participants enrolled in the study engrafted. |
| Arm/Group Title | BEAM + R: Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 |
| Measure Participants | 75 |
| Median (Full Range) [days] |
11
|
| Title | Number of Participants With Overall Best Response Achieved After Transplantation |
|---|---|
| Description | Response was summarized as complete remission (CR): disappearance of all evidence of disease; partial remission (PR): regression of measurable disease (>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses) and no new sites; stable disease (SD): failure to attain CR/PR/PD; relapsed disease or progressive disease (PD): any new lesion or increase by >= 50% of previously involved sites from nadir. |
| Time Frame | 3 months post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis comprised of all participants who received standard BEAM chemotherapy and adjuvant rituximab while undergoing autologous blood stem cell transplantation for high-risk lymphoma or Hodgkin's disease. |
| Arm/Group Title | BEAM + R: Autologous Stem Cell Transplant |
|---|---|
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 |
| Measure Participants | 75 |
| Complete Remission (CR) |
63
84%
|
| Partial Remission (PR) |
8
10.7%
|
| Stable Disease (SD) |
0
0%
|
| Relapsed Disease or Progressive Disease (PD) |
4
5.3%
|
Adverse Events
| Time Frame | Adverse events related to the study drug, rituximab, are reported during the period of 30 days after transplant. | |
|---|---|---|
| Adverse Event Reporting Description | Only related adverse events were collected for this study. | |
| Arm/Group Title | Rituxan+BEAM: Autologous Stem Cell Transplant | |
| Arm/Group Description | Ara-C, VP-16, BCNU, Melphalan, Rituxan and Stem Cells BEAM Conditioning. BEAM Conditioning. Melphalan: Given on Day -1 Melphalan is administered according to the current SOP. Ara-C: 200 mg/m2 IB BID given on Days -5, -4, -3, -2 VP-16: 200 mg/m2 IV BID given on Days -5, -4, -3, -2 BCNU: BCNU 300 mg/m2 IV given on Day -6 Rituxan: 375 mg/m2 IB given on Days -6, +14, +21, +28 Stem Cells: Stem cells given on Day 0 | |
All Cause Mortality |
||
| Rituxan+BEAM: Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Rituxan+BEAM: Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/75 (1.3%) | |
| Infections and infestations | ||
| Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia | 1/75 (1.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Rituxan+BEAM: Autologous Stem Cell Transplant | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/75 (2.7%) | |
| Cardiac disorders | ||
| Cardiovascular/ General - Other | 1/75 (1.3%) | 1 |
| Gastrointestinal disorders | ||
| Stomatitis/pharyngitis (oral/pharyngeal mucositis) | 1/75 (1.3%) | 1 |
| General disorders | ||
| Pain - Other | 1/75 (1.3%) | 1 |
| Infections and infestations | ||
| Infection without neutropenia | 1/75 (1.3%) | 1 |
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 | George Carrum, MD |
|---|---|
| Organization | Baylor College of Medicine |
| Phone | |
| GCarrum@houstonmethodist.org |
- H-11892
- Rituxan+BEAM