High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01534143
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 14.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Other: pharmacological study; Drug: tacrolimus; Drug: sirolimus; Biological: anti-thymocyte globulin; Drug: fludarabine phosphate; Drug: busulfan; Drug: bortezomib; Procedure: allogeneic hematopoietic stem cell transplantation; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

1. 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).

2. 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:

1. Incidence of myeloma progression in this high risk group of patients.

2. Incidence of transplant related mortality and morbidity.

3. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).

4. Incidence and severity of chronic GVHD.

5. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.

6. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.

7. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Other: pharmacological study; Correlative studies; Other Names: pharmacological studies ; Drug: tacrolimus; Given IV; Other Names: FK 506 Prograf ; Drug: sirolimus; Given PO; Other Names: AY 22989 Rapamune rapamycin SLM ; Biological: anti-thymocyte globulin; Given IV; Other Names: ATG ATGAM lymphocyte immune globulin Thymoglobulin ; Drug: fludarabine phosphate; Given IV; Other Names: 2-F-ara-AMP Beneflur Fludara ; Drug: busulfan; Given IV; Other Names: BSF BU Misulfan Mitosan Myeloleukon ; Drug: bortezomib; Given IV; Other Names: LDP 341 MLN341 VELCADE ; Procedure: allogeneic hematopoietic stem cell transplantation; Undergo allogeneic HSCT; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin [First 6 months post-transplant]

   Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.

2. Time to Platelet Absolute Neutrophil Recovery (Engraftment) [First 6 months post-transplant]

   Estimated using Kaplan-Meier method.

3. Treatment Related Mortality Defined as Death in Continuous or Complete Remission [From the date of transplant to the date of death, assessed up to 6 months post transplant]

   Based on National Cancer Institute (NCI) CTCAE version 4.

4. Grade III and IV Non Hematologic Toxicities [First 6 months post transplant]

   Based on NCI CTCAE version 4.

Secondary Outcome Measures

1. Incidence of Myeloma Progression [Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant]

2. Incidence of Transplant Related Mortality and Morbidity [Up to 2 years post transplant]

3. Incidence of TTP [Up to 2 years post transplant]

4. Incidence of SOS [Up to 2 years post transplant]

5. Incidence and Severity of Chronic GVHD [Up to 2 years post transplant]

6. Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation [Weekly to day 100]

7. Overall Survival [Up to 2 years post transplant]

8. Progression Free Survival [From the day of transplant to progression, death, or last contact, assessed up to 2 years]

9. Recovery of T-cell, B Cell and NK Cell Phenotypes [Days 30, 60, 90, and at 6 months after transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to provide informed consent

• Karnofsky Performance Status (KPS) >= 70

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor

• High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:

• Progressive disease after autologous transplant. No less than 3 months post auto transplant

• Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib

• Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics

• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women

Exclusion Criteria:

• Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason

• Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason

• Patient with history of allergy to boron, mannitol, or bortezomib

• Creatinine clearance (CrCl) =< 50 ml/min

• Ejection Fraction < 50%

• Diffusion capacity of carbon monoxide (DLCO) < 50% predicted

• Forced expiratory volume in 1 second (FEV1) < 50% predicted

• Forced vital capacity (FVC) < 50% predicted

• Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator

• Liver enzymes > 3 times upper limit normal

• Bilirubin > 2 mg/dl (except Gilbert's disease)

• International normalized ratio (INR) > 2

• Any previous history of liver failure, hepatitis, or cirrhosis

• Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection

• Grade > I neuropathy

• Women who are pregnant or lactating

• Current or history of alcohol or drug abuse

• Use of other investigational agents within 30 days of enrollment to this study

• Any patient with ascites

• Any patient on home oxygen

• Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT01534143
• Other Study ID Numbers: 2011-151; NCI-2012-00120
• First Posted: Feb 16, 2012
• Last Update Posted: Apr 5, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Sirolimus; Fludarabine; Fludarabine phosphate; Bortezomib; Busulfan; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins

Study Results

Participant Flow

Recruitment Details	Cancer center clinic.

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (0)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
Description	Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.
Time Frame	First 6 months post-transplant

Outcome Measure Data

Analysis Population Description

Data was not collected, because funding was unavailable to continue study.

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

2. Primary Outcome

Title	Time to Platelet Absolute Neutrophil Recovery (Engraftment)
Description	Estimated using Kaplan-Meier method.
Time Frame	First 6 months post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

3. Primary Outcome

Title	Treatment Related Mortality Defined as Death in Continuous or Complete Remission
Description	Based on National Cancer Institute (NCI) CTCAE version 4.
Time Frame	From the date of transplant to the date of death, assessed up to 6 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

4. Primary Outcome

Title	Grade III and IV Non Hematologic Toxicities
Description	Based on NCI CTCAE version 4.
Time Frame	First 6 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

5. Secondary Outcome

Title	Incidence of Myeloma Progression
Time Frame	Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

6. Secondary Outcome

Title	Incidence of Transplant Related Mortality and Morbidity
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

7. Secondary Outcome

Title	Incidence of TTP
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

8. Secondary Outcome

Title	Incidence of SOS
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

9. Secondary Outcome

Title	Incidence and Severity of Chronic GVHD
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

10. Secondary Outcome

Title	Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
Time Frame	Weekly to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

11. Secondary Outcome

Title	Overall Survival
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

12. Secondary Outcome

Title	Progression Free Survival
Time Frame	From the day of transplant to progression, death, or last contact, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

13. Secondary Outcome

Title	Recovery of T-cell, B Cell and NK Cell Phenotypes
Time Frame	Days 30, 60, 90, and at 6 months after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
Measure Participants	0

Adverse Events

Arm/Group Title	Treatment (Chemotherapy, Enzyme Inhibitor)
Arm/Group Description	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
All Cause Mortality
	Treatment (Chemotherapy, Enzyme Inhibitor)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemotherapy, Enzyme Inhibitor)
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Gastrointestinal disorders
Mucositis oral	1/1 (100%)	1
General disorders
Fever	1/1 (100%)	2
Infections and infestations
Staphylococcus bacteremia	1/1 (100%)	1
CMV	1/1 (100%)	1
Nervous system disorders
Headache	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Enzyme Inhibitor)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

Data was not collected, because funding was unavailable to continue study.

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.