Bortezomib and Filgrastim to Promote Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma

Not Applicable

Completed

Conditions: Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Adult Grade III Lymphomatoid Granulomatosis
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma

Interventions: Drug: bortezomib
Biological: filgrastim
Procedure: autologous hematopoietic stem cell transplantation

Registration Number: NCT02037256

Lead Sponsor: Barbara Ann Karmanos Cancer Institute

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:

I. 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.

II. To assess whether time to neutrophil engraftment is 12 days or less, the historical value.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A Treatment (bortezomib and filgrastim)	filgrastim	GROUP A: Bortezomib administered in the evening after comploetion of G-CSF collection or on day 6 of mobilization with G-CSF.
A Treatment (bortezomib and filgrastim)	bortezomib	GROUP A: Bortezomib administered in the evening after comploetion of G-CSF collection or on day 6 of mobilization with G-CSF.
A Treatment (bortezomib and filgrastim)	autologous hematopoietic stem cell transplantation	GROUP A: Bortezomib administered in the evening after comploetion of G-CSF collection or on day 6 of mobilization with G-CSF.
B Treatment (bortezomib and filgrastim)	filgrastim	GROUP B: Bortexomib administered on days 4 \& day 7, before administration of filgrastim.
B Treatment (bortezomib and filgrastim)	autologous hematopoietic stem cell transplantation	GROUP B: Bortexomib administered on days 4 \& day 7, before administration of filgrastim.
B Treatment (bortezomib and filgrastim)	bortezomib	GROUP B: Bortexomib administered on days 4 \& day 7, before administration of filgrastim.

Primary Outcome Measures

Name	Time	Method
>= 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