Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Bortezomib, Autologous, Stem Cell, Purging, In-vivo purging, Ex-vivo purging, Leukapheresis, Contaminated, Stem Cell Harvest, Stem Cell Transplant, Transplantation
Brief summary
Explore stem cell collection with or without bortezomib with in-vivo purging in multiple myeloma.
Detailed description
High dose chemotherapy with autologous stem cell transplant has resulted in improved overall survival and is currently considered an effective first line therapy applicable to the majority of patients with multiple myeloma. However disease relapse is inevitable and remains the primary cause of mortality in this cohort. The purpose of this study is to estimate the proportion of subjects with plasma cell contamination of harvested stem cell product in standard and treatment arms. The study will explore whether or not in-vivo purging of malignant tumor plasma cells will improve progression free survival (PFS) for patients. The study will consist of two groups: Group A: Standard of Care (SOC) stem cell collection without in-vivo purging with bortezomib. Granulocyte colony-stimulating factor (G-CSF) and Mozobil used if needed. Group B: Bortezomib 1.3mg/m\^2 will be given subcutaneously (SQ) on days -11 and -8 followed by Granulocyte colony-stimulating factor (G-CSF) on days -4 through -1 prior to stem cell harvest (day 0).
Interventions
DRUGBortezomib
Bortezomib will be given to Group B participants by injection under the skin 11 days and 8 days before stem cell collection.
Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.
DRUGMozobil
Mozobil will be given to all participants by injection under the skin only if needed per Investigator.
Sponsors
Siddhartha Ganguly
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the inclusion criteria to participate in this study. * Ability to understand, and the willingness to sign a written Informed Consent Form * Diagnosis of multiple myeloma undergoing planned autologous stem cell transplantation * Age ≥ 18 years * Karnofsky Performance Status (KPS) 70 or above, Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 * Adequate organ and marrow function as defined below: * leukocytes ≥ 3,000/micro Liter (mcL) * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcL * total bilirubin within normal institutional limits NOTE: For this study, subjects with bilirubin levels \> 1.5 Upper Limit of Normal (ULN) are excluded from enrollment in this study. * Aspartate Aminotransferase (AST) ( Serum Glutamic Oxaloacetic Transaminase \[SGOT\]) ≤ 2.5 X institutional upper limit of normal * Alanine Aminotransferase (ALT) (Serum Pyruvic Glutamic Transaminase \[SPGT\]) ≤ 2.5 X institutional upper limit of normal * creatinine within normal institutional limits * Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy. Should a woman or partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and the investigator immediately. * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Exclusion criteria
* Subjects meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multiparametric Flow Cytometry - Minimum Residual Disease | Day 0 for all subjects (Day 0 is the day of stem cell collection) | Estimate the proportion of subjects with plasma cell contamination (defined as \>0.01% and at least 100 cellular events) of harvested stem cell product by multi parametric flow cytometry (MFC) from patients with myeloma undergoing autologous stem cell collection 1) by standard of care mobilization using Granulocyte colony-stimulating factor (G-CSF) with or without Mozobil and 2) after two doses of bortezomib as in vivo purging plus standard of care using G-CSF with or without Mozobil. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multiparametric Flow Cytometry - Cluster of Differentiation 34 (CD34)Assessment | Within the first 30 days after stem cell collection | Estimate the proportion of subjects who have a successful collection of stem cells (\> 2 million Cluster of Differentiation 34 (CD34) cells/Kg of body weight) for autologous transplant in both treatment groups. |
| Cluster of Differentiation 34 (CD34) Enumeration | Within the first 30 days after stem cell collection | Estimate the percentage of Cluster of Differentiation 34 (CD34) positive cells in circulating peripheral blood as a measure of mobilization on the days of collection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stem Cell Collection Without In-vivo Purging With Bortezomib Standard of Care Stem cell collection without in-vivo purging with Bortezomib. Standard of Care drugs Granulocyte colony-stimulating factor (G-CSF) +/- Mozobil (the latter if needed).
NOTE: Multiparametric Flow Cytometry to be performed on samples for BOTH groups A and B
Granulocyte colony-stimulating factor (G-CSF): Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.
Mozobil: Mozobil will be given to all participants by injection under the skin only if needed per Investigator. | 51 |
| Stem Cell Collection With In-vivo Purging With Bortezomib Bortezomib will be given subcutaneously (SQ) at 1.3 mg/m2 on day -11 and day -8 followed by Granulocyte colony-stimulating factor (G-CSF) given SQ on day -4 thru day -1 and continued until the collection is completed. Mozobil will be given if needed.
There must be at least 72 hours between each dose of bortezomib. NOTE: Multiparametric Flow Cytometry to be performed on samples for BOTH groups A and B
Bortezomib: Bortezomib will be given to Group B participants by injection under the skin 11 days and 8 days before stem cell collection.
Granulocyte colony-stimulating factor (G-CSF): Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.
Mozobil: Mozobil will be given to all participants by injection under the skin only if needed per Investigator. | 50 |
| Total | 101 |
Baseline characteristics
| Characteristic | Total | Stem Cell Collection Without In-vivo Purging With Bortezomib | Stem Cell Collection With In-vivo Purging With Bortezomib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 14 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants | 37 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 49 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 42 Participants | 21 Participants | 21 Participants |
| Sex: Female, Male Male | 59 Participants | 30 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 51 | 1 / 50 |
| other Total, other adverse events | 39 / 51 | 39 / 50 |
| serious Total, serious adverse events | 12 / 51 | 24 / 50 |
Outcome results
Primary
Multiparametric Flow Cytometry - Minimum Residual Disease
Estimate the proportion of subjects with plasma cell contamination (defined as \>0.01% and at least 100 cellular events) of harvested stem cell product by multi parametric flow cytometry (MFC) from patients with myeloma undergoing autologous stem cell collection 1) by standard of care mobilization using Granulocyte colony-stimulating factor (G-CSF) with or without Mozobil and 2) after two doses of bortezomib as in vivo purging plus standard of care using G-CSF with or without Mozobil.
Time frame: Day 0 for all subjects (Day 0 is the day of stem cell collection)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stem Cell Collection Without In-vivo Purging With Bortezomib | Multiparametric Flow Cytometry - Minimum Residual Disease | 11 Participants |
| Stem Cell Collection With In-vivo Purging With Bortezomib | Multiparametric Flow Cytometry - Minimum Residual Disease | 13 Participants |
Secondary
Cluster of Differentiation 34 (CD34) Enumeration
Estimate the percentage of Cluster of Differentiation 34 (CD34) positive cells in circulating peripheral blood as a measure of mobilization on the days of collection.
Time frame: Within the first 30 days after stem cell collection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stem Cell Collection Without In-vivo Purging With Bortezomib | Cluster of Differentiation 34 (CD34) Enumeration | 8.9 percentage of CD34 positive cells | Standard Deviation 0.1 |
| Stem Cell Collection With In-vivo Purging With Bortezomib | Cluster of Differentiation 34 (CD34) Enumeration | 7.8 percentage of CD34 positive cells | Standard Deviation 0.1 |
Secondary
Multiparametric Flow Cytometry - Cluster of Differentiation 34 (CD34)Assessment
Estimate the proportion of subjects who have a successful collection of stem cells (\> 2 million Cluster of Differentiation 34 (CD34) cells/Kg of body weight) for autologous transplant in both treatment groups.
Time frame: Within the first 30 days after stem cell collection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stem Cell Collection Without In-vivo Purging With Bortezomib | Multiparametric Flow Cytometry - Cluster of Differentiation 34 (CD34)Assessment | 51 Participants |
| Stem Cell Collection With In-vivo Purging With Bortezomib | Multiparametric Flow Cytometry - Cluster of Differentiation 34 (CD34)Assessment | 50 Participants |