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Due to the high rate of morbidity and mortality
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BEAM regimen (BCNU, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for relapsed/refractory lymphoma patients needing autologous stem cell transplantation. Since these components are all effective in myeloma and bortezomib has shown promising results in the transplant setting, here the investigators propose a phase II study to investigate the combination of bortezomib and BEAM as a new conditioning regimen for patients who relapse or progress after the first autologous transplantation and for whom a second autologous transplant is considered.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| V-BEAM + Stem Cell Infusion | Experimental | Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bortezomib | Drug |
|
| |
| Carmustine |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response Rate (Complete Response + Stringent Complete Response) | Defined by the International Myeloma Working Group (IMWG) criteria | Day +100 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Progression-free Survival (PFS) | PFS is defined as the duration from transplant to time of first progression, death, relapse after CR, or the date the patient was last known to be in remission. Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | Median follow-up of 6 months (range: 6.0-12.0 months) |
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Inclusion Criteria:
Patient must have a histologically confirmed diagnosis of multiple myeloma.
Patient must have received a prior autologous stem cell transplantation with melphalan conditioning for multiple myeloma with subsequent disease progression and repeat autologous stem cell transplantation is deemed appropriate by the treating physicians.
Patient must receive induction chemotherapy including 2 to 4 cycles of anti-myeloma therapy including bortezomib, with or without immune modulating agents and/or corticosteroids, Completion of induction therapy will occur within 30 days of first study drug dose.
Patient must have ≥ 2x106/kg CD34+ autologous stem cells available for transplantation.
Patient must be ≥ 18 years of age.
Patient must have life expectancy of greater than 6 months.
Patient must have an ECOG performance status ≤ 2 or Karnofsky performance status ≥ 60% (see Appendices A and B)
Patient must have normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Patient must be able to understand and willing to sign an IRB approved written informed consent document.
Exclusion Criteria:
Inclusion of Women and Minorities
-Both men and women and members of all races and ethnic groups are eligible for this trial.
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| Name | Affiliation | Role |
|---|---|---|
| Ravi Vij, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63122 | United States |
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| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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The study opened to participant enrollment on 09/20/2012 and closed to participant enrollment on 06/18/2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | V-BEAM + Stem Cell Infusion | Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | V-BEAM + Stem Cell Infusion | Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Response Rate (Complete Response + Stringent Complete Response) | Defined by the International Myeloma Working Group (IMWG) criteria | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Number | participants | Day +100 |
|
|
Patients are evaluated from first receiving study treatment until a 30-day follow-up after the conclusion of treatment for adverse events not resulting in death. Adverse events resulting in death will be evaluated through Day +100.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | V-BEAM + Stem Cell Infusion | Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute gout attack | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
2 early deaths caused a concern for safety and resulted in suspension of enrollment in May 2013. After a review of the data, the investigators determined that this regimen had unexpected toxicity & the trial was closed to enrollment in June 2013.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ravi Vij, M.D. | Washington University School of Medicine | 314-454-8304 | rvij@dom.wustl.edu |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| D002330 | Carmustine |
| D005047 | Etoposide |
| D003561 | Cytarabine |
| D008558 | Melphalan |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
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| Drug |
|
|
| Etoposide | Drug |
|
|
| Cytarabine | Drug |
|
|
| Melphalan | Drug |
|
|
| Stem cell infusion | Procedure |
|
| Overall Response Rate (ORR) | ORR includes Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR) Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | 3 months following Day +100 visit |
| Very Good Partial Response Rate (VGPR+nCR+sCR+CR) | Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | Day +100 |
| Toxicity of V-BEAM | Graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients are evaluated from first receiving study treatment until a 30-day follow-up after the conclusion of treatment for adverse events not resulting in death. Adverse events resulting in death will be evaluated through Day +100. This outcomes measures the common toxicities observed. Please refer to the Serious Adverse Event and Other Adverse Event sections of the results for further details. | 30 days after end of treatment / Day +100 |
| Time to Neutrophil Engraftment After V-BEAM. | Time to neutrophil engraftment is defined as duration between Day 0 to the first day of ANC > 0.5x109/L post transplant when it is sustained for more than three consecutive days. | Day +100 |
| Number of Participants With Overall Survival (OS) | OS is defined as the duration from the time of transplant to death or last follow-up. | Median follow-up of 6 months (range: 6-12 months) |
| Treatment Related Mortality (TRM) of V-BEAM | Day +100 |
| Time to Platelet Engraftment After V-BEAM. | Time to platelet engraftment is defined as the duration between Day 0 to the first day of platelet count sustained at > 20x109/L without transfusion. The median time to neutrophil and platelet engraftment will be reported. | Day +100 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Durie-Salmon Stage of Myeloma on Diagnosis | STAGE I
STAGE II -Neither Stage I or Stage III STAGE III
SUBCLASS -A: relatively normal renal function (serum creatinine) <2.0 mg/dL | Number | participants |
|
| International Staging System (ISS) Stage of Myeloma on Diagnosis | STAGE I -Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L) STAGE II -Neither stage I or III STAGE III -Serum beta-2 microglobulin is greater than 5.5 | Number | participants |
|
| Monoclonal Protein Type | Antibodies typically consist of 2 heavy chains and 2 light chains. There are 5 kinds of heavy chains termed IgG, IgA, IgM, IgD, and IgE; and 2 distinct types of light chain, termed kappa and lambda. In myeloma, all the abnormal plasma cells make the same antibody. Therefore the myeloma can be classified by the type of light and heavy chains produced, such as IgG kappa, IgG lambda, IgA kappa, or IgA lambda, etc. Occasionally, the malignant plasma cells make only the light chain component of the antibody. These patients are said to have "light chain myeloma." | Number | participants |
|
| Time to Progression from First Transplant | Median | Full Range | months |
|
| Time from Diagnosis to V-BEAM transplant | Median | Full Range | months |
|
| Number of Prior Therapies (including prior transplant) | Median | Full Range | prior therapies |
|
| Participants |
|
|
| Secondary | Number of Participants With Progression-free Survival (PFS) | PFS is defined as the duration from transplant to time of first progression, death, relapse after CR, or the date the patient was last known to be in remission. Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Number | participants | Median follow-up of 6 months (range: 6.0-12.0 months) |
|
|
|
| Secondary | Overall Response Rate (ORR) | ORR includes Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR) Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Number | participants | 3 months following Day +100 visit |
|
|
|
| Secondary | Very Good Partial Response Rate (VGPR+nCR+sCR+CR) | Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Number | participants | Day +100 |
|
|
|
| Secondary | Toxicity of V-BEAM | Graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients are evaluated from first receiving study treatment until a 30-day follow-up after the conclusion of treatment for adverse events not resulting in death. Adverse events resulting in death will be evaluated through Day +100. This outcomes measures the common toxicities observed. Please refer to the Serious Adverse Event and Other Adverse Event sections of the results for further details. | Posted | Number | participants | 30 days after end of treatment / Day +100 |
|
|
|
| Secondary | Time to Neutrophil Engraftment After V-BEAM. | Time to neutrophil engraftment is defined as duration between Day 0 to the first day of ANC > 0.5x109/L post transplant when it is sustained for more than three consecutive days. | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Median | Full Range | days | Day +100 |
|
|
|
| Secondary | Number of Participants With Overall Survival (OS) | OS is defined as the duration from the time of transplant to death or last follow-up. | Posted | Number | participants | Median follow-up of 6 months (range: 6-12 months) |
|
|
|
| Secondary | Treatment Related Mortality (TRM) of V-BEAM | Posted | Number | participants | Day +100 |
|
|
|
| Secondary | Time to Platelet Engraftment After V-BEAM. | Time to platelet engraftment is defined as the duration between Day 0 to the first day of platelet count sustained at > 20x109/L without transfusion. The median time to neutrophil and platelet engraftment will be reported. | Two participants without evaluable responses due to early mortality were not included in this analysis. | Posted | Median | Full Range | days | Day +100 |
|
|
|
| 4 |
| 10 |
| 10 |
| 10 |
| Febrile neutropenia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Multi-organ failure | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis (death) | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Clostridium difficile positive colitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema - limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Esophageal infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Febrile neutropenia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Group B strep bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Left ventricular systolic dysfunction | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis - oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash (maculo-papular) | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Typhlitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001896 |
| Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Sepsis |
|
| Mucositis (grade 1-2) |
|
| Mucositis (grade 3-4) |
|
| Diarrhea (grade 3-4) |
|
| Hepatic toxicity (grade 3-4) |
|
| Peripheral neuropathy (grade 1-2) |
|
| Toxic death |
|
| Title |
|---|
| Measurements |
|---|
|