Bortezomib and Filgrastim to Promote Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma
Study Details
Study Description
Brief Summary
This clinical trial studies peripheral blood hemapoietic stem cell mobilization with the combination of bortezomib and G-CSF (filgrastim) in multiple myeloma and non-Hodgkin lymphoma patients.
Detailed Description
PRIMARY OBJECTIVES:
-
To estimate if addition of Bortezomib to the mobilization protocol will result with an increase in the levels of circulating peripheral blood stem cells (PBSCs) by at least 2-fold in blood and in the apheresis collections in up to 4-days collection protocol.
-
To assess whether time to neutrophil engraftment is 12 days or less, the historical value.
SECONDARY OBJECTIVES:
-
To test for co-mobilization of lymphoma or myeloma cells by bortezomib and G-CSF using real time polymerase chain reaction (PCR) for non-Hodgkin lymphoma (NHL) patients and by flow cytometry (cluster of differentiation [CD]38+/CD138+ cell) for multiple myeloma (MM) patients.
-
To determine the effect of Bortezomib on the extent of mobilization of dendritic cells subsets, plasmacytoid dendritic cell (pDC)1 and pDC2 and DC1/DC2 ratio by flow cytometry.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A Treatment (bortezomib and filgrastim) GROUP A: Bortezomib administered in the evening after comploetion of G-CSF collection or on day 6 of mobilization with G-CSF. |
Drug: bortezomib
Given IV
Other Names:
Biological: filgrastim
Given SC
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous hematopoietic stem cell transplantation
|
| Experimental: B Treatment (bortezomib and filgrastim) GROUP B: Bortexomib administered on days 4 & day 7, before administration of filgrastim. |
Drug: bortezomib
Given IV
Other Names:
Biological: filgrastim
Given SC
Other Names:
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous hematopoietic stem cell transplantation
|
Outcome Measures
Primary Outcome Measures
- >= 2 Fold Increase in Circulating PBSC's [Up to 6 months]
Participants with >= 2 fold increase in circulating PBSC's in blood and in apheresis collections in up to 4-days collection
Secondary Outcome Measures
- Time to Neutrophil Engraftment [Up to 6 months]
Estimated Median Time to Neutrophil Engraftment, ANC 500
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Voluntary written informed consent form before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
-
Diagnosis of B-type NHL or with multiple myeloma and eligible for autologous transplantation
-
No more than 3 prior regimens of chemotherapy (Rituximab is not considered chemotherapy) and 4 weeks out of Bortezomib treatment for MM
-
Karnofsky performance status of > 50%
-
The patient has recovered from all acute toxic effects of prior chemotherapy
-
White blood cell (WBC) > 3.0 x 10^9/L
-
Absolute neutrophil count > 1.5 x 10^9/L
-
Platelet count > 100 x 10^9/L
-
Serum creatinine =< 2.2
-
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) less than two times the upper limit of normal (ULN)
-
Total bilirubin less than two times the ULN
-
Left ventricle ejection fraction > 50% (by normal echocardiogram [ECHO] or multi gated acquisition scan [MUGA] scan)
-
Diffusing capacity of the lung for carbon monoxide (DLCO) > 50%
-
Forced vital capacity > 50% of predicted
-
Negative for human immunodeficiency virus (HIV)
-
Female subject is either post-menopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential , agree to use 2 effective methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent form through 30 days after the last dose of Bortezomib, or agree to completely abstain from heterosexual intercourse; women of child bearing potential agree to use an approved form of contraception; male subject, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse for the duration of the study
Exclusion Criteria:
-
Patient has a platelet count of < 100x 10^9/L within 14 days before enrollment
-
Patient has an absolute neutrophil count of ANC <1.5 x 10^9/L within 14 days before enrollment
-
Patient has creatinine of > 2.2 MG/DL within 14 days before enrollment
-
Patient has > 1.5 x ULN total bilirubin
-
Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment
-
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
-
Patient has hypersensitivity to Bortezomib, boron or mannitol
-
Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
-
Participation in clinical trials with other investigational drugs not included in this trial, within 14 days before enrollment and throughout the duration of this trial
-
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
-
A co-morbid condition which, in the view of the investigators, renders the patient at high risk for this study
-
An acute medical condition resulting from prior chemotherapy
-
Brain metastases or carcinomatous meningitis
-
Acute infection
-
Fever (temp > 38 degrees Celsius [C]/100.4 degrees Fahrenheit [F])
-
Patients of child-bearing potential unwilling to implement adequate birth control
-
Patients who have deterioration of their clinical status or laboratory parameters between the time of enrollment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician or principal investigator
-
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
-
Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
Sponsors and Collaborators
- Barbara Ann Karmanos Cancer Institute
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Divaya Bhutani, M.D., Barbara Ann Karmanos Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2008-134
- NCI-2012-01173
- 2008-134
- P30CA022453
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | A. Standard of Care Mobilization | GROUP B: Alternative Mobilization |
|---|---|---|
| Arm/Group Description | GROUP A: Standard of care mobiliation: Bortezomib (1.3 mg/m2) in the evening after completion of mobilization with G-CSF | GROUP B: Bortezomib (1.3 mg/m2) IV on days 4 and 7 (if needed) |
| Period Title: Overall Study | ||
| STARTED | 3 | 20 |
| COMPLETED | 3 | 17 |
| NOT COMPLETED | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Arm A | Arm B | Total |
|---|---|---|---|
| Arm/Group Description | Pts. receive filgrastim SC on days 1-9 & begin apheresis on day 5. Pts. undergo apheresis for up to 2 days, & receive bortezomib intravenously (IV) over 3-5 seconds after target collection is obtained with filgrastim alone or on the 1st day of collection with the Bortezomib plus filgrastim mobilization, prior to receiving the administration of filgrastim. 2nd apheresis will continue until target stem cell dose is reached or for maximum 4 days. Pts. undergo autologous hematopoietic stem cell transplantation after receiving high dose chemotherapy & peripheral blood stem cell (PBSC) infusion following standard of care procedures. bortezomib: Given IV filgrastim: Given SC autologous hematopoietic stem cell transplantation: Under | Pts. receive filgrastim SC on days 1-8 & receive bortezomib IV over 3-5 seconds on days 4 & day 7, before administration of filgrastim. Pts. undergo apheresis on days 5-8 | Total of all reporting groups |
| Overall Participants | 3 | 17 | 20 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
66.7%
|
13
76.5%
|
15
75%
|
| >=65 years |
1
33.3%
|
4
23.5%
|
5
25%
|
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
62
|
56
|
58
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
66.7%
|
9
52.9%
|
11
55%
|
| Male |
1
33.3%
|
8
47.1%
|
9
45%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
33.3%
|
3
17.6%
|
4
20%
|
| White |
2
66.7%
|
14
82.4%
|
16
80%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
3
100%
|
17
100%
|
20
100%
|
Outcome Measures
| Title | >= 2 Fold Increase in Circulating PBSC's |
|---|---|
| Description | Participants with >= 2 fold increase in circulating PBSC's in blood and in apheresis collections in up to 4-days collection |
| Time Frame | Up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable patients |
| Arm/Group Title | Group A: Bortezomib 1.3 mg/m2 | Group B Bortezomib 1/3 mg/m2 |
|---|---|---|
| Arm/Group Description | Group A: Bortezomib 1.3 mg/m2 in the evening after completion of 5 day mobilization with G-CSF | Group B Bortezomib 1/3 mg/m2 on day 4 of 5 day GCSF mobilizati |
| Measure Participants | 3 | 17 |
| Doubling |
0
0%
|
4
23.5%
|
| Less than doubling |
3
100%
|
13
76.5%
|
| Title | Time to Neutrophil Engraftment |
|---|---|
| Description | Estimated Median Time to Neutrophil Engraftment, ANC 500 |
| Time Frame | Up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable patients |
| Arm/Group Title | Arm A Standard of Care Mobilization | Arm B Alternative Mobilization |
|---|---|---|
| Arm/Group Description | G-CSF 16 mcg/kg/day for 9 days; Bortezomib 1.3 mg/m2 IV on day 6. Blood draws and apheresis on days 5-9. | G-CSF16 mcg/kg/day for 8 days; Bortezomib on days 4 and 7. Blood collection on days 4 & 8, apheresis on days 5-8. |
| Measure Participants | 3 | 17 |
| Median (95% Confidence Interval) [days to ANC 500] |
12
|
13
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group B Bortezomib 1/3 mg/m2 |
|---|---|---|
| Comments | Median time to engraftment | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | percentage |
| Estimated Value | 0.24 | |
| Confidence Interval |
(2-Sided) 95% 0.07 to 0.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | 6 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | A Treatment (Bortezomib and Filgrastim) | B Treatment (Bortezomib and Filgrastim) | ||
| Arm/Group Description | GROUP A Pts. receive filgrastim SC on days 1-8 & receive bortezomib IV over 3-5 seconds on days 4 & day 7, before administration of filgrastim. Pts. undergo apheresis on days 5-8 bortezomib: Given IV filgrastim: Given SC autologous hematopoietic stem cell transplantation: Under | Group B Pts receive filgrastim SC on days 1-8 and receive bortezomib IV over 3-5 seconds on days 4 and day 7 before administraioin of filgrastim. Pts undergo apheresis on days 5-8. | ||
All Cause Mortality |
||||
| A Treatment (Bortezomib and Filgrastim) | B Treatment (Bortezomib and Filgrastim) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/17 (0%) | ||
Serious Adverse Events |
||||
| A Treatment (Bortezomib and Filgrastim) | B Treatment (Bortezomib and Filgrastim) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/17 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| A Treatment (Bortezomib and Filgrastim) | B Treatment (Bortezomib and Filgrastim) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 17/17 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 0/6 (0%) | 0 | 2/17 (11.8%) | 2 |
| Hypocalcemia | 2/6 (33.3%) | 2 | 3/17 (17.6%) | 3 |
| Hyperuricemia | 1/6 (16.7%) | 1 | 0/17 (0%) | 0 |
| Low ionized calcioum | 0/6 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypokalemia | 0/6 (0%) | 0 | 3/17 (17.6%) | 3 |
| Cardiac disorders | ||||
| Tachycardia | 1/6 (16.7%) | 1 | 0/17 (0%) | 0 |
| Hypertensive crisis | 0/6 (0%) | 0 | 1/17 (5.9%) | 1 |
| Gastrointestinal disorders | ||||
| Vomiting | 0/6 (0%) | 0 | 1/17 (5.9%) | 1 |
| Immune system disorders | ||||
| Mucositis | 0/6 (0%) | 0 | 1/17 (5.9%) | 1 |
| Infections and infestations | ||||
| Infection 1 | 1/6 (16.7%) | 1 | 4/17 (23.5%) | 4 |
| Infection 2 | 0/6 (0%) | 0 | 3/17 (17.6%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 1/6 (16.7%) | 1 | 0/17 (0%) | 0 |
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. Divaya Bhutani |
|---|---|
| Organization | Barbara Ann Karmanos Cancer Institute |
| Phone | 501-680-9229 |
| db3203@cumc.columbia.edu |
- 2008-134
- NCI-2012-01173
- 2008-134
- P30CA022453