Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment

• Sponsor: University of Iowa (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01548573
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 19
• Location: 1
• Arm: 1
• Actual Duration (Months): 27
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By reducing drug resistance, it is hoped that 3-year event-free survival will be increased significantly when compared to Total Therapy II. Additionally, participants will have the option of providing biospecimens for a sub-study evaluating gene expression profiling at specific timepoints to better understand drug-resistance in myeloma, and to determine whether there are genes or gene products in the resistant population that can be targeted by novel therapies.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Dexamethasone; Procedure: Tandem autologous stem cell transplant; Drug: Cisplatin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Bortezomib; Drug: Thalidomide; Drug: Melphalan	Phase 2

Detailed Description

This study is targeted towards patients who have been diagnosed with Multiple Myeloma, POEMS(Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or myeloma plus amyloidosis and have had no more than 12 months of prior treatment. Furthermore, participants cannot have had a prior autologous or allogeneic transplant. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:

• In contrast to Total Therapy II and III, which only allow enrollment of patients with one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of participants with up to 12 months of prior treatment.

• Induction therapy has been reduced to a single cycle.

• Bortezomib and thalidomide have been added to the transplant regimen.

• Carmustine is added to the second transplant.

• Gemcitabine is added to the second transplant regimen.

• Consolidation treatment has been reduced to a single cycle.

• The first year of maintenance consists of 12 28-day cycles of bortezomib,dexamethasone, and either thalidomide, lenalidomide, or cyclophoshamide. The second year of maintenance therapy consists of lenalidomide and dexamethasone.

• The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation, consolidation, and maintenance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tandem Autotransplantation for Multiple Myeloma in Participants With Less Than 12 Months of Preceding Therapy, Incorporating Velcade (Bortezomib) With the Transplant Chemotherapy and During Maintenance
• Actual Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tandem autologous stem cell transplant 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 1: 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) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

Drug: Dexamethasone; Given PO; Other Names: Aeroseb-Dex Decaderm Decadron DM DXM ; Procedure: Tandem autologous stem cell transplant; Drug: Cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP ; Drug: Doxorubicin; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Drug: Cyclophosphamide; Given IV or PO; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: Etoposide; Given IV; Other Names: EPEG VP-16 VP-16-213 Vepesid ; Drug: Bortezomib; Given IV; Other Names: LDP 341 MLN341 VELCADE ; Drug: Thalidomide; Given PO; Other Names: Kevadon Synovir THAL Thalomid ; Drug: Melphalan; Given IV; Other Names: Alkeran CB-3025 L-PAM L-phenylalanine mustard L-Sarcolysin

Outcome Measures

Primary Outcome Measures

1. Event-Free Survival (EFS) [8 years]

   To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.

2. Identification of Drug Resistant Genes [5 years]

   To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.

Secondary Outcome Measures

1. Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens. [2 years]

   To determine whether bortezomib, thalidomide and dexamethasone with transplant 1 and velcade/gemcitabine with transplant 2 can be safely incorporated into well-tested pre-transplant regimens of high-dose melphalan and carmustine/melphalan in doses equivalent to the BEAM(BCNU, etoposide, arabinoside, melphalan)regimen. Treatment-related toxicities will be compared to those reported in the literature using similar intensive approaches.

2. Overall Survival [10 years]

   To determine the median overall survival based on an intent-to-treat analysis, which should exceed 10 years, based on the projected 10-year survival of Total Therapy III, keeping in mind that participants are included in this protocol with up to 12 months of prior therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants must have had a diagnosis of symptomatic MM, MM + amyloidosis, or POEMS (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) requiring treatment. Participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. Note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response.

2. Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory participants are eligible provided the participant has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI.

3. Participants must have received no more than 12 months of prior chemotherapy for this disease. Participants may have received prior radiotherapy provided approval has been obtained from the PI.

4. Participants must not have had a prior transplant.

5. Participants must be 18-80 years of age at the time of study entry.

6. Ejection fraction by ECHO or MUGA of ≥ 40% performed.

7. Participants must have adequate pulmonary function studies, > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete pulmonary function tests due to disease related pain or condition, a participant may still be enrolled provided that the PI or enrolling investigator documents that the participant is a transplant candidate.

8. Participants must have a creatinine < 3 mg/dl and a calculated creatinine clearance

30mL/min. The Cockroft-Gault equation may be used to obtain calculated creatinine clearance.

1. Participants must have a performance status of 0-2 based on ECOG criteria. Participants with a poor performance status (3-4)based solely on bone pain will be eligible, provided there is documentation to verify this.

2. Participants must sign the most current IRB-approved study ICF (Informed Consent Form).

Exclusion Criteria:

1. Prior autologous or allogeneic transplant.

2. Platelet count < 30 x 109/L, unless myeloma-related. If MM-related, the enrolling investigator must document this.

3. grade 3 neuropathy.

4. Known hypersensitivity to bortezomib, boron, or mannitol.

5. Uncontrolled diabetes.

6. Recent (< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.

7. Participants must not have light chain deposition disease-related renal failure or creatinine >3 mg/dl.

8. Participants must not have a concurrent malignancy unless it can be adequately treated by surgical, non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any treatment within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry.

9. Participants must not have life-threatening co-morbidities.

10. Women of child-bearing potential must have a documented negative pregnancy test documented within one week of study entry. Women and men of reproductive potential may not participate unless they have agreed, by signing the study ICF, to use effective contraceptive method(s) as outlined in that form.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

• University of Iowa
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Guido J Tricot, MD, PhD, University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Guido Tricot, Director, Holden Cancer Center Bone Marrow Transplant and Myeloma Program, University of Iowa
• ClinicalTrials.gov Identifier: NCT01548573
• Other Study ID Numbers: 201202818; 7R01CA115399
• First Posted: Mar 8, 2012
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Guido Tricot, Director, Holden Cancer Center Bone Marrow Transplant and Myeloma Program, University of Iowa: multiple myeloma; POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes); amyloidosis; bone marrow transplant; autologous
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan; Doxorubicin; Liposomal doxorubicin; Etoposide; Bortezomib; Etoposide phosphate

Study Results

Participant Flow

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
Period Title: Overall Study
STARTED	19
COMPLETED	14
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 84.2%
>=65 years	3 15.8%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.4
Sex: Female, Male (Count of Participants)
Female	8 42.1%
Male	11 57.9%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival (EFS)
Description	To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.
Time Frame	8 years

Outcome Measure Data

Analysis Population Description

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity). Data for outcome measure 1 were not collected.

Arm/Group Title	Tandem Autologous Stem Cell Transplant
Arm/Group Description	Induction and PBSC Collection:1 cycle of combination D-PACE (and peripheral blood stem cell collection. After collection, participants may receive interim dexamethasone at 20mg days 1-4 every 14 days. Transplant 1: 6 weeks after first day of D-PACE , but can occur as early as 4 weeks and as late as 6 months. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days. Transplant 2: 8 weeks-6 months after the first transplant, participants will have second transplant. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days. Consolidation Phase (if administered): 4 weeks-4 months after second transplant, participants may receive consolidation chemotherapy. Maintenance Phase year 1 and 2:The first year of maintenance will commence between 6 weeks-6 months after consolidation or 4 weeks-6 months after transplant if consolidation is skipped. DP
Measure Participants	0
	0

2. Primary Outcome

Title	Identification of Drug Resistant Genes
Description	To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity). Data for outcome measure 2 were not collected.

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
Measure Participants	0
	0

3. Secondary Outcome

Title	Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens.
Description	To determine whether bortezomib, thalidomide and dexamethasone with transplant 1 and velcade/gemcitabine with transplant 2 can be safely incorporated into well-tested pre-transplant regimens of high-dose melphalan and carmustine/melphalan in doses equivalent to the BEAM(BCNU, etoposide, arabinoside, melphalan)regimen. Treatment-related toxicities will be compared to those reported in the literature using similar intensive approaches.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity). Data for outcome measure 3 were not collected.

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
Measure Participants	0
	0

4. Secondary Outcome

Title	Overall Survival
Description	To determine the median overall survival based on an intent-to-treat analysis, which should exceed 10 years, based on the projected 10-year survival of Total Therapy III, keeping in mind that participants are included in this protocol with up to 12 months of prior therapy.
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity). Data for outcome measure 4 were not collected.

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
Measure Participants	0
	0

Adverse Events

Arm/Group Title	Tandem Transplant in MM <12 Mos of Prior Treatment
Arm/Group Description	This was a single arm study for myeloma patients with <12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.
All Cause Mortality
	Tandem Transplant in MM <12 Mos of Prior Treatment
	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)
Serious Adverse Events
	Tandem Transplant in MM <12 Mos of Prior Treatment
	Affected / at Risk (%)	# Events
Total	13/19 (68.4%)
Blood and lymphatic system disorders
Nausea, failure-to-thrive, and line-associated deep vein thrombosis	1/19 (5.3%)	1
Cardiac disorders
Chest pain, air embolism	1/19 (5.3%)	1
Myocardial infarction	1/19 (5.3%)	1
Atrial Fibrillation with RVR	2/19 (10.5%)	2
Pneumonia, Atrial fib w/ cardioversion	1/19 (5.3%)	1
Gastrointestinal disorders
Cholecystitis	1/19 (5.3%)	1
Nausea, and abdominal pain	1/19 (5.3%)	1
General disorders
Fever	2/19 (10.5%)	2
Neutropenic fever	2/19 (10.5%)	2
Fever	3/19 (15.8%)	3
Malaise and abrupt chest pain	1/19 (5.3%)	1
Neutropenic fever, abdominal pain, and loose stools	1/19 (5.3%)	1
Hypoxia, fever, pulmonary infiltrates with nodules, and C Diff + diarrhea	1/19 (5.3%)	1
Chills, cough, throat pain, dyspnea. Mucositis. + hMPV. Engraftment syndrome	1/19 (5.3%)	1
Infections and infestations
Sepsis	1/19 (5.3%)	1
Viral pneumonia	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/19 (5.3%)	1
Severe back pain	1/19 (5.3%)	1
Nervous system disorders
Stoke secondary to cardio-embolism	1/19 (5.3%)	1
Renal and urinary disorders
Acute kidney injury, uncontrolled hypertension, thrombotic microangiopathy	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/19 (5.3%)	1
Respiratory distress, fevers, and pneumonia	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Tandem Transplant in MM <12 Mos of Prior Treatment
	Affected / at Risk (%)	# Events
Total	19/19 (100%)
Blood and lymphatic system disorders
Anemia	19/19 (100%)	65
Anemia (Hemolytic)	1/19 (5.3%)	1
Bone marrow hypocellularity	1/19 (5.3%)	2
Engraftment fevers	1/19 (5.3%)	1
Febrile Neutropenia	10/19 (52.6%)	10
Other: Platelet refractoriness	1/19 (5.3%)	1
Cardiac disorders
Atrial fibrillation	2/19 (10.5%)	3
Atrial Fibrillation with RVR	1/19 (5.3%)	1
Atrial flutter	1/19 (5.3%)	1
Bradycardia	1/19 (5.3%)	1
chest pain-cardiac	1/19 (5.3%)	1
Left ventricular systolic dysfunction	1/19 (5.3%)	1
myocardial infarction	1/19 (5.3%)	1
Palpitations	1/19 (5.3%)	1
Sinus bradycardia	1/19 (5.3%)	1
Ear and labyrinth disorders
Ear Pain	1/19 (5.3%)	1
Tinnitus	1/19 (5.3%)	1
Eye disorders
Blurred vision	2/19 (10.5%)	2
Gastrointestinal disorders
Abdominal Pain	1/19 (5.3%)	1
Abdominal Pain/discomfort LLQ	1/19 (5.3%)	1
Abdominal Pain/discomfort RUQ	1/19 (5.3%)	1
Bleeding from hemorrhoids	1/19 (5.3%)	1
Bloating	3/19 (15.8%)	3
C-Diff colitis	1/19 (5.3%)	1
Colitis	1/19 (5.3%)	1
Colitis (C-Diff)	1/19 (5.3%)	1
Constipation	7/19 (36.8%)	14
Diarrhea	10/19 (52.6%)	11
Diarrhea (c diff pos)	3/19 (15.8%)	4
Diarrhea (C Diff Neg)	8/19 (42.1%)	8
Diarrhea (C Diff)	2/19 (10.5%)	3
Diarrhea/loose stools	1/19 (5.3%)	1
Dry mouth	2/19 (10.5%)	2
Dysphagia	2/19 (10.5%)	2
Dyspnea	8/19 (42.1%)	12
Enterocolitis	1/19 (5.3%)	1
Esophagitis	1/19 (5.3%)	1
Esophagitis (CMV related)	1/19 (5.3%)	1
Gastritis	1/19 (5.3%)	2
Gastroenteritis	1/19 (5.3%)	1
Gastro-esophageal reflux	2/19 (10.5%)	3
GERD with Barrett's esophagus	1/19 (5.3%)	1
Mucositis	1/19 (5.3%)	1
Mucositis (morphine prn)	1/19 (5.3%)	1
Mucositis (oral)	1/19 (5.3%)	1
Mucositis (oral) requiring TPN	1/19 (5.3%)	1
Mucositis oral	4/19 (21.1%)	7
Mucositis oral (cvn + pca narcotics)	1/19 (5.3%)	1
Nausea	11/19 (57.9%)	24
Nausea with dexamethasone	1/19 (5.3%)	1
Nausea/vomiting (from post-nasal drip)	1/19 (5.3%)	1
Nausea/Vomiting (TPN)	1/19 (5.3%)	1
Oral pain (tongue lesion)	1/19 (5.3%)	1
Stomach pain	1/19 (5.3%)	1
Stomach pain (not during dex admin)	1/19 (5.3%)	1
Vomiting	5/19 (26.3%)	9
General disorders
Ankle edema	1/19 (5.3%)	1
Bilateral edema in limbs	1/19 (5.3%)	1
Bleeding at port site	1/19 (5.3%)	1
Dizziness	8/19 (42.1%)	10
Dizziness (orthostatic hypotension)	1/19 (5.3%)	1
Edema	1/19 (5.3%)	1
Edema (feet)	1/19 (5.3%)	1
Edema in left lower ankle	1/19 (5.3%)	1
Edema Limbs	1/19 (5.3%)	1
Edema limbs (bilateral)	1/19 (5.3%)	1
Edema limbs (legs)	1/19 (5.3%)	1
Engraftment fever	1/19 (5.3%)	1
Engraftment fevers controlled with steroids	1/19 (5.3%)	1
Fatigue	13/19 (68.4%)	26
Fever	1/19 (5.3%)	1
Fever (non-neutropenic)	5/19 (26.3%)	6
Gait Disturbance	1/19 (5.3%)	1
Gait disturbance (d/t dizziness)	1/19 (5.3%)	1
Infusion Site Extravasation w bruising, no pain	1/19 (5.3%)	1
Localized edema (leg)	1/19 (5.3%)	1
Localized edema (right leg) w/out DVT	1/19 (5.3%)	1
Malaise	1/19 (5.3%)	1
Multi-organ failure	1/19 (5.3%)	1
Neutropenic fever	1/19 (5.3%)	1
Non-cardiac chest pain	2/19 (10.5%)	2
Non-cardiac pleuritic chest pain	1/19 (5.3%)	1
Other: Failure to thrive	2/19 (10.5%)	2
Pain at port and catheter site	1/19 (5.3%)	1
Swelling of right hand (neg doppler)	1/19 (5.3%)	1
Weakness	2/19 (10.5%)	4
Hepatobiliary disorders
Cholecystitis (w/ gallstone present)	1/19 (5.3%)	1
Gallbladder sludge	1/19 (5.3%)	1
Immune system disorders
Cytokine release syndrome	1/19 (5.3%)	1
Engraftment syndrome	2/19 (10.5%)	2
Infections and infestations
Catheter related infection	1/19 (5.3%)	1
Catheter related infection: enterococcal (vanc sensitive)	2/19 (10.5%)	2
Catheter-related infection	1/19 (5.3%)	1
catheter-related infection (gram+ cocci)	1/19 (5.3%)	1
Catheter-related infection (VRE)	1/19 (5.3%)	1
Catheter-related infection: enterococcal (vanc sensitive)	1/19 (5.3%)	1
CMV Reactivation	1/19 (5.3%)	1
Coag neg staph bacteremia x 3	1/19 (5.3%)	1
HHV 6 viremia reactivation	1/19 (5.3%)	1
Laryngitis	1/19 (5.3%)	1
Lip infection (HSV)	1/19 (5.3%)	1
Lung infection: fungal pneumonia	1/19 (5.3%)	1
Lung infection: left lower lobe consolidation	1/19 (5.3%)	1
Lung infection: pneumonia	2/19 (10.5%)	2
Lung infection: pneumonia (hMPV and staph)	1/19 (5.3%)	1
Lung infection: Pulmonary infiltrates with nodules	1/19 (5.3%)	1
Lung infection: RSV Pneumonia	1/19 (5.3%)	1
Lung Infection: serratia marcescens	1/19 (5.3%)	1
Lung infection: viral pneumonia	1/19 (5.3%)	1
Lung infections: CMV pneumonia	1/19 (5.3%)	1
Lymphopenic fever	1/19 (5.3%)	1
Other: CMV reactivation	1/19 (5.3%)	1
Other: VRE + coag neg staph bacteremia (Enterococcus faecium)	1/19 (5.3%)	1
Otitis media	1/19 (5.3%)	1
Pansinusitis	1/19 (5.3%)	1
Pharyngitis	1/19 (5.3%)	1
Sepsis	1/19 (5.3%)	1
Sepsis (Gram Neg)	1/19 (5.3%)	1
Toe infection	1/19 (5.3%)	1
Vancomycin-Resistant Enterococcus	2/19 (10.5%)	2
Injury, poisoning and procedural complications
Bruising on abdomen and arms	1/19 (5.3%)	1
Left Rib Fracture	1/19 (5.3%)	1
Vascular Access Complication (air embolism)	1/19 (5.3%)	1
Investigations
Activated PTT prolonged	1/19 (5.3%)	2
Alanine aminotransferase increased	4/19 (21.1%)	4
Allergic reaction during PBSC Collection	1/19 (5.3%)	1
ALT increased	5/19 (26.3%)	6
AST increased	4/19 (21.1%)	4
Creatinine increased	2/19 (10.5%)	4
Lymphocyte count decreased	19/19 (100%)	31
Neutrophil count decreased	1/19 (5.3%)	1
Other: sub-therapeutic INR	1/19 (5.3%)	1
Other: Vanc sensitive Enterococcal + coag neg staph bacteremia	1/19 (5.3%)	1
Platelet count decreased	19/19 (100%)	65
PTT prolonged	1/19 (5.3%)	1
Serum amylase increased	1/19 (5.3%)	1
WBC decreased	19/19 (100%)	56
Weight Loss	3/19 (15.8%)	4
Metabolism and nutrition disorders
Anorexia	5/19 (26.3%)	8
Hypercalcemia	1/19 (5.3%)	1
Hyperglycemia	1/19 (5.3%)	14
Hyperglycemia (Dex)	9/19 (47.4%)	15
Hypernatremia	4/19 (21.1%)	4
Hyperuricemia	2/19 (10.5%)	2
Hypoalbuminemia	7/19 (36.8%)	9
Hypocalcemia	18/19 (94.7%)	42
Hypoglycemia	1/19 (5.3%)	2
Hypokalemia	12/19 (63.2%)	22
Hypomagnesemia	1/19 (5.3%)	1
Hypophosphatemia	16/19 (84.2%)	31
Iron overload	1/19 (5.3%)	1
Other: Chloride increased	1/19 (5.3%)	1
Other: CO2 decreased	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Back Pain	4/19 (21.1%)	5
Bilateral Calf Pain at time of engraftment	1/19 (5.3%)	1
Bone pain	2/19 (10.5%)	2
Bone/joint pain	1/19 (5.3%)	1
Generalized muscle weakness	3/19 (15.8%)	3
Generalized bone pain	1/19 (5.3%)	1
Hip pain	1/19 (5.3%)	1
Hyponatremia	6/19 (31.6%)	7
Joint pain right knee	1/19 (5.3%)	1
joint pains in right hip and shoulder	1/19 (5.3%)	1
Low back and hip pain	1/19 (5.3%)	1
Lower back pain	2/19 (10.5%)	2
Minor left leg pain	1/19 (5.3%)	1
Other, muscle spasms in lower back and neck	1/19 (5.3%)	1
Pain	2/19 (10.5%)	2
Pain in both elbows	1/19 (5.3%)	1
Pain in extremity (left lower arm)	1/19 (5.3%)	1
Pain in hips and left lower leg	1/19 (5.3%)	1
Pain in lower back	1/19 (5.3%)	1
Rib pain	1/19 (5.3%)	1
Rt knee joint pain w/ swelling	1/19 (5.3%)	1
Nervous system disorders
Akathisia (restless feet)	1/19 (5.3%)	1
Dygeusia (abnormal taste)	1/19 (5.3%)	1
Dysgeusia	1/19 (5.3%)	1
Dysgeusia (altered taste)	1/19 (5.3%)	1
Hand tremor	1/19 (5.3%)	1
Headache	5/19 (26.3%)	7
Headache with dexamethasone	1/19 (5.3%)	1
Left hemiparesis	1/19 (5.3%)	1
Paresthesia	1/19 (5.3%)	1
Peripheral Neuropathy	4/19 (21.1%)	7
Peripheral Neuropathy (feet)	1/19 (5.3%)	2
Peripheral neuropathy (hands)	1/19 (5.3%)	1
Peripheral Neuropathy (thal held)	1/19 (5.3%)	1
Peripheral Neuropathy (thalidomide stopped)	1/19 (5.3%)	1
Peripheral Neuropathy (toes)	1/19 (5.3%)	1
Somnolence	3/19 (15.8%)	3
Stroke	1/19 (5.3%)	1
Syncope	2/19 (10.5%)	2
Tremor	1/19 (5.3%)	1
Tremor in hands, R> L	2/19 (10.5%)	2
Psychiatric disorders
Anxiety	1/19 (5.3%)	2
Confusion	1/19 (5.3%)	1
Delirium	3/19 (15.8%)	3
Hallucinations (with voriconazole)	1/19 (5.3%)	1
Insomnia	1/19 (5.3%)	1
Insomnia (Dex)	5/19 (26.3%)	5
Renal and urinary disorders
Acute kidney injury	1/19 (5.3%)	1
Urinary Frequency	1/19 (5.3%)	1
Urinary Frequency (Nocturnal)	1/19 (5.3%)	1
Urinary Incontinence	1/19 (5.3%)	3
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome	2/19 (10.5%)	2
aspiration	1/19 (5.3%)	1
Cough	1/19 (5.3%)	1
Dysnea	1/19 (5.3%)	1
Hypoxia	5/19 (26.3%)	5
Laryngeal inflammation	1/19 (5.3%)	1
Nasal congestion	1/19 (5.3%)	1
Pleural Effusion	2/19 (10.5%)	2
Pneumonitis	1/19 (5.3%)	1
Pneumonitis (hMPV)	1/19 (5.3%)	1
Post-nasal drip	1/19 (5.3%)	1
Pulmonary Edema	4/19 (21.1%)	4
Respiratory failure/ARDS	1/19 (5.3%)	1
Sore Throat	2/19 (10.5%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis (excessive perspiration)	1/19 (5.3%)	1
Maculopapular rash	1/19 (5.3%)	1
Rash	2/19 (10.5%)	2
Rash - face and neck	1/19 (5.3%)	1
Rash maculo-papular	1/19 (5.3%)	1
Scalp Pain	1/19 (5.3%)	1
Vascular disorders
Flushing	1/19 (5.3%)	1
Hypertension	3/19 (15.8%)	5
Hypotension	5/19 (26.3%)	5
Hypotension with PBSC infusion	1/19 (5.3%)	1
Orthostatic Hypotension	1/19 (5.3%)	1
Other: Left carotid artery stenosis	1/19 (5.3%)	1

Limitations/Caveats

Enrollment halted prematurely. Study met stopping rules. Outcomes will not be tracked and published

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.