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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-00120 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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Data was not collected, because funding was unavailable to continue study.
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells
PRIMARY OBJECTIVES:
I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).
2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).
3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).
SECONDARY OBJECTIVES:
I. Incidence of myeloma progression in this high risk group of patients.
II. Incidence of transplant related mortality and morbidity.
III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).
IV. Incidence and severity of chronic GVHD.
V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.
I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.
After completion of study treatment, patients are followed up for up to 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, enzyme inhibitor) | Experimental | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pharmacological study | Other | Correlative studies |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin | Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method. | First 6 months post-transplant |
| Time to Platelet Absolute Neutrophil Recovery (Engraftment) | Estimated using Kaplan-Meier method. | First 6 months post-transplant |
| Treatment Related Mortality Defined as Death in Continuous or Complete Remission | Based on National Cancer Institute (NCI) CTCAE version 4. | From the date of transplant to the date of death, assessed up to 6 months post transplant |
| Grade III and IV Non Hematologic Toxicities | Based on NCI CTCAE version 4. | First 6 months post transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Myeloma Progression | Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant | |
| Incidence of Transplant Related Mortality and Morbidity | Up to 2 years post transplant |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Zaid Al-Kadhimi | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
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Cancer center clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Chemotherapy, Enzyme Inhibitor) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. anti-thymocyte globulin : Given IV pharmacological study : Correlative studies fludarabine phosphate : Given IV busulfan : Given IV bortezomib : Given IV allogeneic hematopoietic stem cell transplantation : Undergo allogeneic HSCT tacrolimus : Given IV laboratory biomarker analysis : Correlative studies sirolimus : Given PO |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| tacrolimus | Drug | Given IV |
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| sirolimus | Drug | Given PO |
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| anti-thymocyte globulin | Biological | Given IV |
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| fludarabine phosphate | Drug | Given IV |
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| busulfan | Drug | Given IV |
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| bortezomib | Drug | Given IV |
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| allogeneic hematopoietic stem cell transplantation | Procedure | Undergo allogeneic HSCT |
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| laboratory biomarker analysis | Other | Correlative studies |
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| Incidence of TTP | Up to 2 years post transplant |
| Incidence of SOS | Up to 2 years post transplant |
| Incidence and Severity of Chronic GVHD | Up to 2 years post transplant |
| Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation | Weekly to day 100 |
| Overall Survival | Up to 2 years post transplant |
| Progression Free Survival | From the day of transplant to progression, death, or last contact, assessed up to 2 years |
| Recovery of T-cell, B Cell and NK Cell Phenotypes | Days 30, 60, 90, and at 6 months after transplant |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Chemotherapy, Enzyme Inhibitor) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. anti-thymocyte globulin : Given IV pharmacological study : Correlative studies fludarabine phosphate : Given IV busulfan : Given IV bortezomib : Given IV allogeneic hematopoietic stem cell transplantation : Undergo allogeneic HSCT tacrolimus : Given IV laboratory biomarker analysis : Correlative studies sirolimus : Given PO |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin | Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method. | Data was not collected, because funding was unavailable to continue study. | Posted | First 6 months post-transplant |
|
| |||||||||||||||||||
| Primary | Time to Platelet Absolute Neutrophil Recovery (Engraftment) | Estimated using Kaplan-Meier method. | Posted | First 6 months post-transplant |
|
| ||||||||||||||||||||
| Primary | Treatment Related Mortality Defined as Death in Continuous or Complete Remission | Based on National Cancer Institute (NCI) CTCAE version 4. | Posted | From the date of transplant to the date of death, assessed up to 6 months post transplant |
|
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| Primary | Grade III and IV Non Hematologic Toxicities | Based on NCI CTCAE version 4. | Posted | First 6 months post transplant |
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| Secondary | Incidence of Myeloma Progression | Posted | Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant |
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| Secondary | Incidence of Transplant Related Mortality and Morbidity | Posted | Up to 2 years post transplant |
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| Secondary | Incidence of TTP | Posted | Up to 2 years post transplant |
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| Secondary | Incidence of SOS | Posted | Up to 2 years post transplant |
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| Secondary | Incidence and Severity of Chronic GVHD | Posted | Up to 2 years post transplant |
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| Secondary | Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation | Posted | Weekly to day 100 |
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| Secondary | Overall Survival | Posted | Up to 2 years post transplant |
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| Secondary | Progression Free Survival | Posted | From the day of transplant to progression, death, or last contact, assessed up to 2 years |
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| |||||||||||||||||||||
| Secondary | Recovery of T-cell, B Cell and NK Cell Phenotypes | Posted | Days 30, 60, 90, and at 6 months after transplant |
|
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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 | Treatment (Chemotherapy, Enzyme Inhibitor) | CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. anti-thymocyte globulin : Given IV pharmacological study : Correlative studies fludarabine phosphate : Given IV busulfan : Given IV bortezomib : Given IV allogeneic hematopoietic stem cell transplantation : Undergo allogeneic HSCT tacrolimus : Given IV laboratory biomarker analysis : Correlative studies sirolimus : Given PO | 1 | 1 | 0 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mucositis oral | Gastrointestinal disorders |
| |||
| Fever | General disorders |
| |||
| Staphylococcus bacteremia | Infections and infestations |
| |||
| CMV | Infections and infestations |
| |||
| Headache | Nervous system disorders |
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Data was not collected, because funding was unavailable to continue study.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Zaid Al-Kahdimi, M.D. | Barbara Ann Karmanos Cancer Institute | (313) 576-8022 | zalkadh@emory.edu |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| 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 |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D020123 | Sirolimus |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| C042382 | fludarabine phosphate |
| D002066 | Busulfan |
| D000069286 | Bortezomib |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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