Neoplasms

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Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

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Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Vincristine

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Tubulin Modulators

Antimitotic Agents

Vincristine, DOXIL (doxorubicin HCl liposomal injection), and Dexamethasone (VDD) vs. Vincristine, Doxorubicin and Dexamethasone (VAD)

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

The purpose of this study is to determine how well newly diagnosed multiple myeloma patients respond to an experimental regimen of Vincristine, DOXIL (doxorubicin HCl liposome injection) and Dexamethasone (VDD) versus the standard treatment of Vincristine, Doxorubicin and Dexamethasone (VAD).

This is a randomized, open label study comparing the efficacy, clinical benefit, toxicity and safety of the combination of Vincristine, DOXIL® (doxorubicin HCl liposome injection), and Dexamethasone (VDD) to the standard regimen of Vincristine, Doxorubicin and Dexamethasone (VAD) in patients with newly diagnosed multiple myeloma. Approximately 200 patients with newly diagnosed multiple myeloma will be randomized to receive either VDD or VAD. This study will determine and compare the objective response rate (the percentage of patients who attain an Objective Status of Complete Remission, Remission or Partial Remission) for patients receiving VDD vs. VAD. This study will also evaluate and compare the clinical benefit of VDD vs. VAD for the following measures: Hospitalization; Documented sepsis; Antibiotic use; Grade 3 or 4 neutropenia or neutropenic fever.

VDD: Vincristine 1.4 mg/m2 IV on Day 1; Doxil® 40 mg/m2 IV on Day 1; Dexamethasone 40 mg/day oral Days 1-4; VAD: Vincristine 0.4 mg/day continuous infusion Days 1-4; Doxorubicin 9.0 mg/m2/day continuous infusion Days 1-4; Dexamethasone 40 mg/day orally on Days 1-4; Every 28 days for 4 cycles

Vincristine, DOXIL (Doxorubicin HCl Liposome Injection) and Dexamethasone vs. Vincristine, Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

A Multi-Center Randomized Study of Vincristine, Doxil and Dexamethasone vs. Vincristine, Doxorubicin, and Dexamethasone in Patients With Multiple Myeloma

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Fludarabine

Fludarabine phosphate

Melphalan

Lenograstim

Bortezomib

Myeloma Proteins

Paraproteins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Allogeneic Stem Cell Transplant: Fludarabine+Melphalan+Bortezomib followed by Allogeneic Rescue.

Autologous Stem Cell Transplant: Melphalan+Bortezomib followed by Autologous Rescue.

Group B Expansion on Bortezomib Maintenance: Autologous Only.

AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

Autologous Stem Cell Transplant

Days -6,-5,-4,-3 Fludarabine 30 mg/m\^2/day IV

Allogeneic Stem Cell Transplant: Allogeneic Peripheral Blood Stem Cell Rescue. Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients. Allogeneic donor stem cells may also be cryopreserved if they cannot be infused fresh.

Allogeneic Stem Cell Transplant

Melissa Alsina, MD

Jose Ochoa-Bayona, MD

The purpose of this study is to evaluate the effectiveness of Bortezomib when added to standard chemotherapy medicine(s) for treatment of Multiple Myeloma.

The primary objectives of this study are:

* To determine the 2 year-progression free survival in multiple myeloma with an allogeneic transplant using a conditioning regimen of melphalan + fludarabine + Bortezomib in patients \< 60 years of age and available HLA-matched donor and compare it with the 2 year-progression-free-survival after an autologous stem cell transplant with melphalan+Bortezomib conditioning in patients \< 60 years.
* To determine the 2 year-progression free survival in multiple myeloma with an autologous stem cell transplant using a conditioning regimen of melphalan + Bortezomib. for patients \> 60 years of age and patients \< 60 years of age who decline allogeneic stem cell transplant.

The secondary objectives of this study are:

* To determine the overall survival in multiple myeloma with autologous or allogeneic stem cell transplants using the above conditioning regimens
* To determine the response rates in multiple myeloma using the above regimens.
* To determine minimal residual disease status using allele specific oligonucleotides (ASO-PCR) by PCR and flow-cytometry for multiple myeloma cells.
* To correlate minimal residual disease status with 2 year progression free survival and overall survival.
* To determine the incidence of acute and chronic graft-versus-host disease (GVHD) in multiple myeloma with allogeneic stem cell transplant using the above conditioning regimen.
* To examine quality of life in patients treated with allogeneic and autologous stem cell transplants using the above conditioning regimen.

Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma

Evaluation of Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma After Cytoreductive Therapy

Percentage of participants with Acute or Chronic GVHD following transplant

PFS: Number of participants, per treatment arm with progression free survival at time of analysis. Survival time will be measured from the date of transplant to the date of progression, death or the last follow-up, whichever comes first. Progressive Disease (PD): Increase of ≥ 25% from lowest response value in any one or more of the following: Serum M-component and/or; Urine M-component and/or; Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL; Bone marrow plasma cell percentage; absolute percentage ≥ 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder.

Overall survival in participants with multiple myeloma treated with Bortezomib (Velcade®) containing conditioning regimen and autologous as well as allogeneic transplantation.

Complete Response according to International Myeloma Working Group uniform response criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

Millennium Pharmaceuticals, Inc.

H. Lee Moffitt Cancer Center and Research Institute

All Serious Adverse Events are reported, regardless of causality. For this study that includes patients undergoing hematopoietic cell transplantation (HCT), review and consideration was given for reporting of Other Adverse Events that are designated in the protocol as commonly observed after HCT. Patients are monitored for Serious Adverse Events and Other Adverse events beginning at on treatment date. Patients who did not receive treatment: not included in at risk numbers.

A: Allogeneic Stem Cell Transplant

B: Autologous Stem Cell Transplant

BE: Group B Expansion

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline: All participants enrolled on study. Adverse Events: All participants who received study treatment. Outcome Measures: All participants evaluable at time of analysis.

SAEs not recorded for participants off study, though they were followed for survival.

Dr. Melissa Alsina

All participants evaluable at time of analysis

Progression Free Survival (PFS)

Allogeneic Stem Cell Transplant: Fludarabine+Melphalan+Bortezomib followed by Allogeneic Rescue.

Bortezomib: AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan: AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Fludarabine: Days -6,-5,-4,-3 Fludarabine 30 mg/m\^2/day IV

Allogeneic Stem Cell Transplant: Allogeneic Peripheral Blood Stem Cell Rescue. Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with granulocyte colony-stimulating factor (GCSF) mobilization and infused fresh to recipients. Allogeneic donor stem cells may be cryopreserved if they cannot be infused

Autologous Stem Cell Transplant: Melphalan+Bortezomib followed by Autologous Rescue.

Bortezomib: AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan: AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Autologous Stem Cell Transplant: Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

Group B Expansion on Bortezomib Maintenance: Autologous Only.

Bortezomib: AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan: AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Autologous Stem Cell Transplant: Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

Overall Survival (OS) Rate

Patients were in very good partial response at the time on enrollment without sufficient plasma cells in bone marrow to be able to perform assay for molecular response.

Molecular Complete Response (CR) Rates in Patients With Multiple Myeloma

Allogenic Stem Cell Transplant: Fludarabine + Melphalan + Bortezomib followed by Allogenic Rescue

A: Allogenic Stem Cell Transplant

Allogenic Stem Cell Transplant patients only. Autologous patients do not suffer from GVHD.

Percentage of Participants With Acute or Chronic Graft-versus-host Disease (GVHD) Following Transplant

Overall Study

Plasmacytoma

Thalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Athanasios Fassas, MD

The purpose of this study is to evaluate the use of thalidomide for the treatment of cancer. Patients with many types of cancers will be enrolled because the researchers will also study how the different cancers respond and what kind of side effects patients will experience.

Angiogenesis is a normal, physiological process in the growing embryo, wound healing and ovulation. Progressive recruitments of blood vessels to the tumor site are thought to result in a self perpetuating loop helping to drive the growth of tumors. This new vasculature also allows competent tumor cells to find access to the vascular system and facilitate distant spread of tumor cells. Neovascularization is apparently an absolute prerequisite for physical expansion of solid tumors to grow beyond the volume of about 1-2 mm in diameter. Several molecular and cellular mechanisms have been identified by which tumor parenchyma may exert its angiogenic effect on host endothelial cells. There is also evidence that endothelial cells themselves, like other stromal cells, may act reciprocally to alter the behavior of adjacent tumor cells in a paracrine or cell contact mediated fashion. There is now known to be a diverse family of angiogenic growth factors, foremost among them being basic FGF and VEGF. Several angiogenic peptide genes have been sequenced and cloned. The degree of vascularization has acquired importance as an independent prognostic indicator in various types of solid tumors. More recently, it has been noted that increased angiogenesis may also be an important feature in hematologic malignancies, e.g. leukemia.

An Open Protocol for the Compassionate Use of Thalidomide

An Open Protocol For The Compassionate Use of Thalidomide For Patients With Advanced Or Refractory Malignancies

University of Arkansas

Bevacizumab

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

Immunoglobulin M

Immunoglobulin A

Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

David S Siegel, MD, PhD

The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.

Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.

Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.

Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.

There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed Refractory Multiple Myeloma

Study Schema: Bortezomib will be administered on Days 1. 4, 8, and 11. Response will be assessed subsequent to each 21-day cycle. Progression is defined using the Bladé criteria, defined progression as an increase of \>25% in paraprotein or urinary light chain excretion (or marrow plasma cell percentage in the marrow

The secondary objective of this study is to assess the safely and tolerability of the combination treatment of bevacizumnab and bortezomnib. Adjustments in the dosing schedule of bortezomib would be made for patients with adequate response as per Blade criteria and continue until disease progression or 18 months

Genentech, Inc.

Hackensack Meridian Health

Overall Survival (OS) - Overall Survival is Calculated at the Time of the Screening Evaluation to Death From Any Cause.

Drug Combination

Age, Categorical

7 subjects were consented 6 proceeded with treatment, 4 completed study: one failed screening and one was dropped due to non-compliance with protocol, one withdrew consent

The study was terminated prior to enrollment completion and formal analysis of the primary objectives was never conducted.

Dr. David Siegel

Bortezomib and Bevacizumab

Median Number of Cycles to Tumor Progression (TTP)

Bortezomilb will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vincristine, DOXIL (Doxorubicin HCl Liposome Injection) and Dexamethasone vs. Vincristine, Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma	NCT00344422	Multiple Myelom... Myeloma M-Protein Myeloma Protein...	Vincristine, DO...	18 Years -	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma	NCT00948922	Multiple Myelom...	Bortezomib Melphalan Autologous Stem... Fludarabine Allogeneic Stem...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma	NCT00948922	Multiple Myelom...	Bortezomib Melphalan Autologous Stem... Fludarabine Allogeneic Stem...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
An Open Protocol for the Compassionate Use of Thalidomide	NCT00081757	Multiple Myelom...	Thalidomide	18 Years -	University of Arkansas
Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma	NCT00948922	Multiple Myelom...	Bortezomib Melphalan Autologous Stem... Fludarabine Allogeneic Stem...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Vincristine, DOXIL (Doxorubicin HCl Liposome Injection) and Dexamethasone vs. Vincristine, Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma	NCT00344422	Multiple Myelom... Myeloma M-Protein Myeloma Protein...	Vincristine, DO...	18 Years -	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma	NCT00464178	Multiple Myelom...	Bortezomib	18 Years -	Hackensack Meridian Health
An Open Protocol for the Compassionate Use of Thalidomide	NCT00081757	Multiple Myelom...	Thalidomide	18 Years -	University of Arkansas

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