Autologous or Syngeneic Stem Cell Transplant Followed by Donor Stem Cell Transplant and Bortezomib in Treating Patients With Newly Diagnosed High-Risk, Relapsed, or Refractory Multiple Myeloma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00793572
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 96
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial studies the side-effects and anti-cancer effects of giving an autologous or syngeneic stem cell transplant followed by an allogeneic donor stem cell transplant and bortezomib. Patients treated on this trial have newly diagnosed high-risk, relapsed, or refractory multiple myeloma (MM). Giving chemotherapy before an autologous stem cell transplant slows or stops the growth of cancer cells by preventing them from dividing or killing them. Stem cells that were harvested earlier from the patient's blood and frozen are then returned to the patient to replace the blood-forming cells that were destroyed by chemotherapy. Giving chemotherapy and total-body irradiation before an allogeneic donor stem cell transplant also prevents the patient's immune system from rejecting the donor's stem cells. Undergoing an autologous or syngeneic stem cell transplantation followed by an allogeneic donor stem cell transplant and bortezomib may be overall more effective in killing cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Refractory Plasma Cell Myeloma	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Bortezomib; Drug: Cyclosporine; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Syngeneic Bone Marrow Transplantation; Radiation: Total-Body Irradiation	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Progression-free survival (PFS) at 2 years after the autograft (=< 50% in historic controls).

SECONDARY OBJECTIVES:

1. Overall survival (OS) at 2 years after the autograft.

2. Non-relapse mortality (NRM) at 200 days and 1 year after allograft.

3. Incidence of grades II-IV acute graft-versus-host-disease (GVHD) and chronic extensive GVHD.

4. Safety of bortezomib maintenance therapy after stem cell transplantation.

OUTLINE:

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Patients undergo PBSC mobilization and collection using the preferred regimens at the participating institution.

CONDITIONING CHEMOTHERAPY AND AUTOLOGOUS OR SYNGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients receive high-dose melphalan intravenously (IV) on day -2 followed by an autologous or syngeneic HSCT on day 0.

NON-MYELOABLATIVE ALLOGENEIC HSCT: Beginning 40-180 days after autologous HSCT, patients receive 1 of the following regimens:

1. HLA-IDENTICAL RELATED DONOR: Patients receive cyclosporine IV or orally (PO) twice daily (BID) starting on days -3 to 56, and taper until day 180. Patients then undergo total-body irradiation (TBI) and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive mycophenolate mofetil (MMF) PO BID on days 0-27.

2. HLA-UNRELATED DONOR: Patients receive fludarabine phosphate IV on days -4 to -2. Patients also receive cyclosporine IV or PO BID starting on days -3 to 100 and taper until day 180. Patients then undergo TBI and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive MMF PO thrice daily (TID) on days 0-27 and then BID on days 27-40 with taper of MMF on days 40-96.

MAINTENANCE THERAPY: Beginning 60-120 days after allogeneic HSCT, patients receive bortezomib subcutaneously (SC) on days 1 and 4 of 14-day cycles for 9 months or for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then annually for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tandem Autologous HCT/Nonmyeloablative Allogeneic HCT From HLA-Matched Related and Unrelated Donors Followed by Bortezomib Maintenance Therapy for Patients With High-Risk Multiple Myeloma
• Actual Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy See Detailed Description

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo transplantation; Other Names: Autologous Stem Cell Transplantation ; Drug: Bortezomib; Given SC; Other Names: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade ; Drug: Cyclosporine; Given IV; Other Names: 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Neoral OL 27-400 Sandimmun Sandimmune SangCya ; Drug: Cyclosporine; Given PO; Other Names: 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Neoral OL 27-400 Sandimmun Sandimmune SangCya ; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara Oforta SH T 586 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Drug: Mycophenolate Mofetil; Given PO; Other Names: Cellcept MMF ; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Undergo transplantation; Other Names: Non-myeloablative allogeneic transplant Nonmyeloablative Stem Cell Transplantation NST ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo transplantation; Other Names: PBPC transplantation Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplantation ; Procedure: Syngeneic Bone Marrow Transplantation; Undergo transplantation; Radiation: Total-Body Irradiation; Undergo radiotherapy; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation

Outcome Measures

Primary Outcome Measures

1. Number of Patients Surviving Progression-free [At 2 years after the autograft]

   Number of subjects surviving without progressive disease post-transplant. Progressive disease criteria: Greater than 25% increase in serum (absolute increase must be ≥0.5 g/dL) or urine (absolute increase must be ≥200 mg/24h) M proteins compared to best response status after autologous transplant. Appearance of new lytic bone lesions or plasmacytomas.

Secondary Outcome Measures

1. Number of Patients With Grade II-IV Acute GVHD [100 days post allo transplant]

   Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: - a maculopapular eruption involving < 25% BSA - a maculopapular eruption involving 25 - 50% BSA - generalized erythroderma - generalized erythroderma w/ bullous formation and often w/ desquamation Liver: - bilirubin 2.0 - 3.0 mg/100 mL - bilirubin 3 - 5.9 mg/100 mL - bilirubin 6 - 14.9 mg/100 mL - bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death

2. Number of Patients With Chronic GVHD [1 year post allo]

   Number of subjects with classic chronic or chronic extensive GVHD post allogeneic transplant.

3. Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy [Up to 100 days after the autograft or allograft]

   Number of subjects with toxicities related to bortezomib maintenance therapy post-transplant.

4. Number of Patients With Non-relapse Mortality [200 and 365 days after allo]

   Number of subjects with non-relapse mortalities post allogeneic transplant.

5. Number of Patients Surviving Overall [At 2 years after the autograft]

   Number of subjects surviving two years post autologous transplant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Newly diagnosed patients must have received induction therapy (e.g., vincristine, doxorubicin, dexamethasone [VAD], thalidomide/dexamethasone) for a minimum of 4 cycles

• Must have the capacity to give informed consent

• Must have an human leukocyte antigen (HLA) genotypically identical sibling or a phenotypically matched relative or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search

• In addition, patients must meet at least one of the criteria A-I (A-G at time of diagnosis or pre-autograft):

• 1. Any abnormal karyotype by metaphase analysis except for isolated t(11,14) and constitutional cytogenetic abnormality
• 1. Fluorescence in situ hybridization (FISH) translocation 4;14
• 1. FISH translocation 14;16
• 1. FISH deletion 17p
• 1. Beta2-microglobulin > 5.5 mg/L
• 1. Cytogenetic hypodiploidy
• 1. Plasmablastic morphology (>= 2%)

• DONOR: HLA genotypically identical sibling or phenotypically matched relative OR

• DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria, Grade #2.1)

• Matched HLA-A, B, C, DRB1, and DQB1 alleles by high resolution typing.

• Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing

Exclusion Criteria:

• Recurrent or non-responsive (less than partial response [PR]) MM after at least two different lines of conventional chemotherapy

• Progressive MM after a previous autograft

• Life expectancy severely limited by disease other than malignancy

• Seropositive for the human immunodeficiency virus (HIV)

• Females who are pregnant or breastfeeding

• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy

• Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month

• Patients with the following organ dysfunction:

• Symptomatic coronary artery disease or ejection fraction < 40% or other cardiac failure requiring therapy; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

• Ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease

• Diffusing lung capacity for carbon monoxide (DLCO) < 50%, forced expiratory volume in 1 second (FEV) < 50% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) principle investigator (PI) of the study must approve of enrollment of all patients with pulmonary nodules

• Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin > 3 mg/dL; and symptomatic biliary disease;

• Karnofsky score < 70% for adult patients

• Patient with poorly controlled hypertension and on multiple antihypertensives

• Patients with current >= grade 2 peripheral neuropathy

• Patient has an active bacterial or fungal infection unresponsive to medical therapy

• DONOR: Identical twin

• DONOR: Donors unwilling to donate PBSC

• DONOR: Pregnancy

• DONOR: Infection with HIV

• DONOR: Inability to achieve adequate venous access

• DONOR: Known allergy to G-CSF

• DONOR: Current serious systemic illness

• DONOR: Failure to meet FHCRC criteria for stem cell donation

• DONOR: Age < 12 years

• DONOR: A positive anti-donor cytotoxic crossmatch

• DONOR: Patient and donor pairs must not be homozygous at mismatched allele

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• Millennium Pharmaceuticals, Inc.
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marco Mielcarek, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marco Mielcarek, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00793572
• Other Study ID Numbers: 2070.00; NCI-2009-01473; MPI X05251; 2070.00; P30CA015704
• First Posted: Nov 19, 2008
• Last Update Posted: Jan 22, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Bortezomib; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Period Title: Overall Study
STARTED	32
COMPLETED	32
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 93.8%
>=65 years	2 6.3%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49.2
Sex: Female, Male (Count of Participants)
Female	14 43.8%
Male	18 56.3%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Surviving Progression-free
Description	Number of subjects surviving without progressive disease post-transplant. Progressive disease criteria: Greater than 25% increase in serum (absolute increase must be ≥0.5 g/dL) or urine (absolute increase must be ≥200 mg/24h) M proteins compared to best response status after autologous transplant. Appearance of new lytic bone lesions or plasmacytomas.
Time Frame	At 2 years after the autograft

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
Count of Participants [Participants]	14 43.8%

2. Secondary Outcome

Title	Number of Patients With Grade II-IV Acute GVHD
Description	Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: - a maculopapular eruption involving < 25% BSA - a maculopapular eruption involving 25 - 50% BSA - generalized erythroderma - generalized erythroderma w/ bullous formation and often w/ desquamation Liver: - bilirubin 2.0 - 3.0 mg/100 mL - bilirubin 3 - 5.9 mg/100 mL - bilirubin 6 - 14.9 mg/100 mL - bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Time Frame	100 days post allo transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
Count of Participants [Participants]	14 43.8%

3. Secondary Outcome

Title	Number of Patients With Chronic GVHD
Description	Number of subjects with classic chronic or chronic extensive GVHD post allogeneic transplant.
Time Frame	1 year post allo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
Count of Participants [Participants]	10 31.3%

4. Secondary Outcome

Title	Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy
Description	Number of subjects with toxicities related to bortezomib maintenance therapy post-transplant.
Time Frame	Up to 100 days after the autograft or allograft

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
Count of Participants [Participants]	1 3.1%

5. Secondary Outcome

Title	Number of Patients With Non-relapse Mortality
Description	Number of subjects with non-relapse mortalities post allogeneic transplant.
Time Frame	200 and 365 days after allo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
200 days post allo	1 3.1%
1 Year post allo	1 3.1%

6. Secondary Outcome

Title	Number of Patients Surviving Overall
Description	Number of subjects surviving two years post autologous transplant.
Time Frame	At 2 years after the autograft

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
Measure Participants	32
Count of Participants [Participants]	21 65.6%

Adverse Events

Time Frame	AEs: Conditioning through Day 100 post Auto; SAEs: Conditioning through Day 200 post Auto
Arm/Group Title	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
Arm/Group Description	See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo transplantation Bortezomib: Given SC Cyclosporine: Given IV Cyclosporine: Given PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo transplantation Peripheral Blood Stem Cell Transplantation: Undergo transplantation Syngeneic Bone Marrow Transplantation: Undergo transplantation Total-Body Irradiation: Undergo radiotherapy
All Cause Mortality
	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
	Affected / at Risk (%)	# Events
Total	16/32 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	1/32 (3.1%)	1
Blood and lymphatic system disorders, Other (Microangiopathy)	1/32 (3.1%)	1
Cardiac disorders
Chest pain - cardiac	1/32 (3.1%)	1
Gastrointestinal disorders
Enterocolitis	1/32 (3.1%)	1
Gastric hemorrhage	1/32 (3.1%)	1
Lower gastrointestinal hemorrhage	1/32 (3.1%)	1
Nausea	4/32 (12.5%)	4
Obstruction gastric	1/32 (3.1%)	1
General disorders
Fatigue	1/32 (3.1%)	1
Fever	3/32 (9.4%)	3
Multi-organ failure	1/32 (3.1%)	1
Non-cardiac chest pain	1/32 (3.1%)	1
Immune system disorders
GVHD	3/32 (9.4%)	3
Infections and infestations
Bronchial infection	2/32 (6.3%)	2
Mucosal infection	1/32 (3.1%)	1
Sepsis	1/32 (3.1%)	1
Sinusitis	1/32 (3.1%)	1
Upper respiratory infection	1/32 (3.1%)	1
Infections and infestations, Other (Serum)	1/32 (3.1%)	1
Nervous system disorders
Headache	2/32 (6.3%)	2
Renal and urinary disorders
Acute kidney injury	2/32 (6.3%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/32 (3.1%)	1
Vascular disorders
Thromboembolic event	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
	Affected / at Risk (%)	# Events
Total	13/32 (40.6%)
Blood and lymphatic system disorders
Febrile neutropenia	3/32 (9.4%)	3
Cardiac disorders
Atrial fibrillation	2/32 (6.3%)	2
Left ventricular dysfunction	1/32 (3.1%)	1
Pericardial effusion	1/32 (3.1%)	1
Pericardial tamponade	1/32 (3.1%)	1
Supraventricular tachycardia	1/32 (3.1%)	1
Gastrointestinal disorders
Colitis	1/32 (3.1%)	1
Diarrhea	1/32 (3.1%)	1
Mucositis oral	4/32 (12.5%)	5
Investigations
Blood bilirubin increased	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/32 (3.1%)	1
Hypoxia	2/32 (6.3%)	3
Vascular disorders
Hypotension	1/32 (3.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.