Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Muneer Abidi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT02037256
First received: January 14, 2014
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.


Condition Intervention
Adult Grade III Lymphomatoid Granulomatosis
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Contiguous Stage II Marginal Zone Lymphoma
Contiguous Stage II Small Lymphocytic Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Progressive Hairy Cell Leukemia, Initial Treatment
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage I Adult Burkitt Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Mixed Cell Lymphoma
Stage I Adult Diffuse Small Cleaved Cell Lymphoma
Stage I Adult Immunoblastic Large Cell Lymphoma
Stage I Adult Lymphoblastic Lymphoma
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage I Small Lymphocytic Lymphoma
Stage II Multiple Myeloma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Untreated Hairy Cell Leukemia
Waldenström Macroglobulinemia
Drug: bortezomib
Biological: filgrastim
Procedure: autologous hematopoietic stem cell transplantation

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Peripheral Blood Hematopoietic Stem Cell Mobilization With the Combination of Bortezomib and G-CSF in Multiple Myeloma and Non-Hodgkin's Lymphoma Patients

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Increase in levels of circulating PBSC by at least two-fold in the blood and in the apheresis collections in a 4-day collection protocol [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    All analyses will be descriptive and exploratory. The shape of the frequency distributions of each of the endpoints will be examined graphically and analytically to determine the appropriate statistical analyses. Paired comparisons will be made using t-tests and box plots will be used to describe each of the endpoints. Estimates will be made with 95% confidence limits.

  • Neutrophil engraftment [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    All analyses will be descriptive and exploratory. The shape of the frequency distributions of each of the endpoints will be examined graphically and analytically to determine the appropriate statistical analyses. Paired comparisons will be made using t-tests and box plots will be used to describe each of the endpoints. Estimates will be made with 95% confidence limits.


Secondary Outcome Measures:
  • Co-mobilization of lymphoma or myeloma cells by bortezomib and filgrastim [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    All analyses will be descriptive and exploratory. The shape of the frequency distributions of each of the endpoints will be examined graphically and analytically to determine the appropriate statistical analyses. Paired comparisons will be made using t-tests and box plots will be used to describe each of the endpoints. Estimates will be made with 95% confidence limits.

  • Mobilization of dendritic cell subsets pDCI and pDC2 and the ratio DC1/DC2 [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    All analyses will be descriptive and exploratory. The shape of the frequency distributions of each of the endpoints will be examined graphically and analytically to determine the appropriate statistical analyses. Paired comparisons will be made using t-tests and box plots will be used to describe each of the endpoints. Estimates will be made with 95% confidence limits.


Estimated Enrollment: 20
Study Start Date: July 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib and filgrastim)

GROUP A: Patients receive filgrastim SC on days 1-9 and begin apheresis on day 5. Patients undergo apheresis for up to 2 days, and receive bortezomib intravenously (IV) over 3-5 seconds after target collection is obtained with filgrastim alone or on the first day of collection with the Bortezomib plus filgrastim mobilization, prior to receiving the administration of filgrastim. Second apheresis will continue until target stem cell dose is reached or for maximum 4 days. Patients undergo autologous hematopoietic stem cell transplantation after receiving high dose chemotherapy and peripheral blood stem cell (PBSC) infusion following standard of care procedures.

GROUP B: Patients receive filgrastim SC on days 1-8 and receive bortezomib IV over 3-5 seconds on days 4 and day 7, before administration of filgrastim. Patients undergo apheresis on days 5-8. (See Detailed Description)

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous hematopoietic stem cell transplantation

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if addition of Bortezomib to the mobilization protocol will result with an increase in the levels of circulating peripheral blood stem cells (PBSCs) by >= 2-fold in blood and in the apheresis collections in up to 4-days collection protocol.

II. To achieve median neutrophil engraftment of 12 days.

SECONDARY OBJECTIVES:

I. 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.

II. 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.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

GROUP A: Patients receive filgrastim subcutaneously (SC) on days 1-9 and begin apheresis on day 5. Patients undergo apheresis for up to 2 days, and receive bortezomib intravenously (IV) over 3-5 seconds after target collection is obtained with filgrastim alone or on the first day of collection with the Bortezomib plus filgrastim mobilization, prior to receiving the administration of filgrastim. Second apheresis will continue until target stem cell dose is reached or for maximum 4 days. Patients undergo autologous hematopoietic stem cell transplantation after receiving high dose chemotherapy and peripheral blood stem cell (PBSC) infusion following standard of care procedures.

GROUP B: Patients receive filgrastim SC on days 1-8 and receive bortezomib IV over 3-5 seconds on days 4 and day 7, before administration of filgrastim. Patients undergo apheresis on days 5-8. Within 2 months after mobilization, patients undergo autologous hematopoietic stem cell transplantation after receiving high dose chemotherapy and PBSC infusion as is the standard of care.

After completion of study treatment, patients are followed at 1 month and 6 months.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02037256

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Muneer Abidi Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Muneer Abidi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT02037256     History of Changes
Other Study ID Numbers: 2008-134, NCI-2012-01173, 2008-134, P30CA022453
Study First Received: January 14, 2014
Last Updated: May 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Leukemia
Waldenstrom Macroglobulinemia
Lymphoma, Extranodal NK-T-Cell
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
Intraocular Lymphoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on October 01, 2014