Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Monoclonal Gammopathy of Undetermined Significance

Precancerous Conditions

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

beta alethine

Suzin Mayerson, PhD

RATIONALE: Biological therapies such as beta alethine use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Phase I/II trial to study the effectiveness of beta alethine in treating patients who have myeloma.

OBJECTIVES:

* Determine the antitumor effects of low-dose beta alethine in patients with myeloma or progressive monoclonal gammopathy of undetermined significance.
* Determine the effects of this regimen on anemia, performance status, pain, and delayed-type hypersensitivity (immune response) in these patients.
* Determine the safety of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive beta alethine subcutaneously every 2 weeks for 6 doses. At day 85, patients may receive an additional 12-week course of therapy in the absence of disease progression or unacceptable toxicity. Patients with an apparent complete response receive additional courses.

Patients are followed for 2 weeks.

PROJECTED ACCRUAL: A total of 13-37 patients will be accrued for this study.

Beta Alethine in Treating Patients With Myeloma

Phase I/II Study to Assess the Safety and Efficacy of Low Doses of Beta LT in Patients With Myeloma

LifeTime Pharmaceuticals

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Infections

Recurrence

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Amyloidosis

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Immunoglobulin Light-chain Amyloidosis

Lymphoma, B-Cell

Burkitt Lymphoma

Waldenstrom Macroglobulinemia

Leukemia, Hairy Cell

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Lymphatic Diseases

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

AL Amyloidosis

Hairy Cell Leukemia

Lymphoma, Large-cell, Immunoblastic

Antineoplastic Agents

All Drugs and Chemicals

Bortezomib

Proteasome Inhibitors

bortezomib

Alex A. Adjei, MD, PhD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of PS-341 in treating patients who have advanced cancer.

OBJECTIVES:

* Determine the maximum tolerated dose and toxicity of PS-341 in patients with advanced malignancies.
* Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

* Regimen A: Patients receive PS-341 IV twice weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3-4 or 2 of 6 patients experience dose-limiting toxicity.

* Regimen B: Once the MTD has been determined in regimen A, patients receive PS-341 IV twice weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 14 months.

PS-341 in Treating Patients With Advanced Cancer

A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders

National Cancer Institute (NCI)

Mayo Clinic

Alex A. Adjei, M.D.

Proteostasis Deficiencies

Metabolic Diseases

Light Chain Deposition Disease

Anti-Infective Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Amino Acids

Thalidomide

Dexamethasone

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Melphalan

Cisplatin

Dexamethasone acetate

BB 1101

Etoposide phosphate

Mechlorethamine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Phenylalanine

Induction : DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.

After collection, participants will receive dexamethasone x 4 days every 14 days.

Transplant: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.

Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.

Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide)

Maintenance: Year 1 - VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

dexamethasone

cisplatin

doxorubicin

cyclophosphamide

etoposide

thalidomide

melphalan

autologous stem cell transplant

Margarida Magalhaes-Silverman, MD

This phase II trial investigates whether patients greater than or equal to 65 years of age diagnosed with myeloma or another plasma cell malignancy will have better outcomes with transplant followed by maintenance therapy, as primarily measured by progression-free survival, versus non-transplant approaches.

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) from the start of dexamethasone, cisplatin, Adriamycin (doxorubicin),Cytoxan (cyclophosphamide), etoposide (DPACE) for all participants who have had at least one day of protocol treatment.

II. To evaluate how well such therapy is tolerated in patients mainly over the age of 65 years by assessing severe complications (intensive care unit \[ICU\] admission, death) and the percentage of participants able to complete the full course of therapy.

SECONDARY OBJECTIVES:

I. To evaluate Quality-Of-Life post-transplant using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30 and QLC-MY20.

OUTLINE:

INDUCTION THERAPY: Patients receive dexamethasone orally (PO) on days 1-4 and 8-11, cisplatin intravenously (IV) continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV, and etoposide IV on days 1-4. Patients then receive pegfilgrastim subcutaneously (SQ) on days 6 and 13 and undergo collection of stem cells when white blood cell (WBC) and cluster of differentiation (CD)34 counts are within program range. Following stem cell collection, patients may receive interim dexamethasone PO on days 1-4, every 14 days at the discretion of the treating physician.

TRANSPLANT: Beginning between 4 weeks to 6 months after the first day of induction therapy, patients receive as transplant conditioning regimen dexamethasone PO on days -4 to -1 and days +2 through +5, bortezomib IV bolus on days -4, -1, 2, and 5, thalidomide PO on days -4 to 5, and melphalan IV on days -4 and -1. Patients undergo autologous peripheral blood stem cell transplant (PBSCT) on day 0. Between transplant and consolidation therapy, patients receive dexamethasone PO on days 1-4 every 21 days and thalidomide PO daily.

CONSOLIDATION THERAPY: If administered, post-transplant consolidation may begin 4-6 weeks after transplant but should occur no more than 4 months later. Most patients will not receive consolidation. Those that do will receive dexamethasone PO on days 1-4 and 8-11, thalidomide PO on days 1-11, bortezomib IV on days 1, 4, 8, and 11, cisplatin IV continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV continuously, and etoposide IV continuously on days 1-4.

MAINTENANCE THERAPY YEAR 1: Beginning 6 weeks-6 months after consolidation therapy or 4 weeks to 6 months after transplant if consolidation is skipped, patients receive bortezomib IV bolus on days 1, 4, 15, and 18, thalidomide PO QD on days 1-28, and dexamethasone PO on days 1-4 and 15-18. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY YEAR 2: Patients receive bortezomib IV on days 1, 4, 15, and 18, cyclophosphamide PO or IV on days 1 and 15, and dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least once annually at the study center, but serum for MM marker results will be sent to the study site for close monitoring of PFS .

Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

Single Autologous Transplant Followed by Consolidation and Maintenance for Participants ≥ 65 Years of Age Diagnosed With Multiple Myeloma or a Related Plasma Cell Malignancy

PFS is defined as the time from the start of DPACE to the date of first documentation of disease progression as assessed by the International Myeloma Working Group response criteria or death due to any cause. Progression is defined using the International Myeloma Working Group response criteria, an increase of greater than or equal to 25% from the lower response value.

Percentage of participants with severe complications defined at ICU admission and death, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Percentage of participants able to complete the full course of therapy.

Measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and Multiple Myeloma module (QLQ-MY20). The EORTC QLQ-C30 includes functional scales (physical, role, emotional, cognitive, and social) and global health status. The EORTC QLQ-MY20 includes disease symptoms and treatment side effects scales. Scores are averaged and transformed to 0-100 scale. For functional and global health status, a positive change from baseline (pre-DPACE) indicates improvement whereas for the symptom scales a negative change from baseline (pre-DPACE) indicates improvement.

Margarida Magalhaes-Silverman

Principal Investigator

Adverse events (AEs ≥ grade 3) were recorded. AEs were not recorded by start and stop date but by phase of treatment in which the AE occurred. AEs will be recorded as the worst grade achieved during that phase of treatment.

Initial chemotherapy will consist of 1 cycle of combination D-PACE chemotherapy and peripheral blood stem cell collection.

D-PACE/Induction

Following D-PACE and Peripheral Blood Stem Cell (PBSC) collection, participants may receive interim dexamethasone at 20mg days 1-4 every 14 days, but this may be omitted by the treating physician

Post D-PACE/Pre-Transplant

Transplant should preferably occur 6 weeks after the induction PACE continuous infusion has been completed, but can occur as early as 4 weeks and as late as 3 months if the participant fails to mobilize stem cells after the PACE administration

Transplant

Participants will receive dexamethasone 20 mg oral days 1-4 every 21 days and thalidomide 100 mg oral and daily in the interim between transplant and consolidation.

If administered, post-transplant consolidation therapy should begin 4-6 weeks after transplant, but should occur no later than 4 months after transplant. Consolidation will consist of one cycle of VDT-PACE.

Post-transplant/Consolidation

Maintenance will begin 4 weeks to 6 months after transplant, or between 6 weeks to 6 months after consolidation if administered. This is considered standard of care

Maintenance Therapy, Year 1

Maintenance Therapy, Year 2

Study participants will be evaluated at the study center at least once per year.

Long Term Follow-up

Induction : DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.

After collection, participants will receive dexamethasone x 4 days every 14 days.

Transplant: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.

Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.

Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide)

Maintenance: Year 1 - VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

dexamethasone: Given PO

cisplatin: Given IV

doxorubicin: Given IV

cyclophosphamide: Given IV or PO

etoposide: Given IV

bortezomib: Given IV

thalidomide: Given PO

melphalan: Given IV

autologous stem cell transplant

Autologous Stem Cell Transplant

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Participants who have had at least one day of protocol treatment.

Median Progression Free Survival (mPFS)

Participants who have had at least one day of protocol treatment

Percentage of Participants With Serious Treatment-Related Complications

Participants who received at least one day of study treatment

Percentage of Participants Able to Complete Full Course Therapy

Change in Physical Functioning at Pre-Maintenance

Change in Physical Functioning at Maintenance Cycle 6

Change in Physical Functioning at Maintenance Cycle 12

Change in Physical Functioning at Maintenance Cycle 18

Change in Physical Functioning at Maintenance Cycle 24

Change in Role Functioning at Pre-Maintenance

Change in Role Functioning at Maintenance Cycle 6

Change in Role Functioning at Maintenance Cycle 12

Change in Role Functioning at Maintenance Cycle 18

Change in Role Functioning at Maintenance Cycle 24

Change in Emotional Functioning at Pre-Maintenance

Change in Emotional Functioning at Maintenance Cycle 6

Change in Emotional Functioning at Maintenance Cycle 12

Change in Emotional Functioning at Maintenance Cycle 18

Change in Emotional Functioning at Maintenance Cycle 24

Change in Cognitive Functioning at Pre-Maintenance

Change in Cognitive Functioning at Maintenance Cycle 6

Change in Cognitive Functioning at Maintenance Cycle 12

Change in Cognitive Functioning at Maintenance Cycle 18

Change in Cognitive Functioning at Maintenance Cycle 24

Change in Social Functioning at Pre-Maintenance

Change in Social Functioning at Maintenance Cycle 6

Change in Social Functioning at Maintenance Cycle 12

Change in Social Functioning at Maintenance Cycle 18

Change in Social Functioning at Maintenance Cycle 24

Change in Global Health Status at Pre-Maintenance

Change in Global Health Status at Maintenance Cycle 6

Change in Global Health Status at Maintenance Cycle 12

Change in Global Health Status at Maintenance Cycle 18

Change in Global Health Status at Maintenance Cycle 24

Change in Distress Symptoms at Pre-Maintenance

Change in Distress Symptoms at Maintenance Cycle 6

Change in Distress Symptoms at Maintenance Cycle 12

Change in Distress Symptoms at Maintenance Cycle 18

Change in Distress Symptoms at Maintenance Cycle 24

Change in Side Effects of Treatment at Pre-Maintenance

Change in Side Effects of Treatment at Maintenance Cycle 6

Change in Side Effects of Treatment at Maintenance Cycle 12

Change in Side Effects of Treatment at Maintenance Cycle 18

Change in Side Effects of Treatment at Maintenance Cycle 24

Participants who received at least one day of study treatment. Globally, there were 37 patients who were included in at least one of the estimated mean change scores being reported. Four patients were not included due to not completing the baseline questionnaire making it impossible to calculate change from baseline (n=3) or did not complete the questionnaire at any time point (n=1).

Mean Change in Quality-Of-Life Indicators Post-Transplant

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Beta Alethine in Treating Patients With Myeloma	NCT00006466	Multiple Myelom... Precancerous Co...	beta alethine	18 Years -	National Cancer Institute (NCI)
PS-341 in Treating Patients With Advanced Cancer	NCT00006362	Leukemia Lymphoma Multiple Myelom... Precancerous Co... Unspecified Adu...	bortezomib	18 Years -	Mayo Clinic
Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma	NCT01849783	Extramedullary ... Isolated Plasma... Light Chain Dep... Primary Systemi... Stage I Multipl... Stage II Multip... Stage III Multi...	dexamethasone cisplatin doxorubicin cyclophosphamid... etoposide bortezomib thalidomide melphalan autologous stem...	65 Years - 85 Years	University of Iowa
Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma	NCT01849783	Extramedullary ... Isolated Plasma... Light Chain Dep... Primary Systemi... Stage I Multipl... Stage II Multip... Stage III Multi...	dexamethasone cisplatin doxorubicin cyclophosphamid... etoposide bortezomib thalidomide melphalan autologous stem...	65 Years - 85 Years	University of Iowa
Beta Alethine in Treating Patients With Myeloma	NCT00006466	Multiple Myelom... Precancerous Co...	beta alethine	18 Years -	National Cancer Institute (NCI)
S0340 MRI and Fludeoxyglucose F18 PET in Diagnosing Solitary Plasmacytoma	NCT00109889	Multiple Myelom... Plasmacytoma	magnetic resona... positron emissi...	18 Years - 120 Years	SWOG Cancer Research Network
S0340 MRI and Fludeoxyglucose F18 PET in Diagnosing Solitary Plasmacytoma	NCT00109889	Multiple Myelom... Plasmacytoma	magnetic resona... positron emissi...	18 Years - 120 Years	SWOG Cancer Research Network
SWOG-9239 Reduction of Immunosuppression Plus Interferon Alfa and Combination Chemotherapy in Treating Patients With Malignant Tumors That Develop After Organ Transplant	NCT00002657	Lymphoma Multiple Myelom...	bleomycin sulfa... recombinant int... cyclophosphamid... cytarabine doxorubicin hyd... etoposide methotrexate prednisone vincristine sul... conventional su... radiation thera...	15 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for isolated plasmacytoma of bone