Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00381940
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 120
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and efficacy of bortezomib with ifosfamide and vinorelbine in children and young adults with Hodgkin's lymphoma that was recurrent or did not respond to previous therapy. Bortezomib is an inhibitor of protein degradation. Bortezomib degrades short-lived regulatory proteins in the cell, and has been reported to increase the tumor cells. Bortezomib may increase the effectiveness of ifosfamide and vinorelbine (two standard drugs given to children with Hodgkin Lymphoma that has come back after initial treatment) by making cancer cells more sensitive to effectiveness of standard chemotherapy by preventing anti-death responses in these drugs. Giving bortezomib together with ifosfamide and vinorelbine tartrate should kill more cancer cells than are killed with ifosfamide and vinorelbine alone.

Condition or Disease	Intervention/Treatment	Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Childhood Lymphocyte Depletion Hodgkin Lymphoma; Childhood Lymphocyte Predominant Hodgkin Lymphoma; Childhood Mixed Cellularity Hodgkin Lymphoma; Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma; Childhood Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Childhood Hodgkin Lymphoma	Drug: ifosfamide; Drug: bortezomib; Drug: vinorelbine tartrate; Biological: filgrastim	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the efficacy and safety of bortezomib (as a chemosensitizing agent) in pediatric patients and young adults with primary refractory Hodgkin's lymphoma (HL) or HL in first relapse.

2. Determine the response rate in patients treated with bortezomib, ifosfamide, and vinorelbine ditartrate (vinorelbine tartrate) (IVB) and compare the response rate to the historical response rate in patients treated with ifosfamide and vinorelbine ditartrate alone.

SECONDARY OBJECTIVES:

1. Determine the overall response rate (complete and partial response) and induction success rate after 2 or 4 courses of therapy and the reinduction rate (complete response) after 4 courses of therapy.

2. Determine the proportion of patients able to mobilize sufficient hematopoietic stem cells (CD34+) after 2 courses of IVB.

OUTLINE: This is a multicenter, open-label, pilot study.

Patients receive ifosfamide intravenously (IV) continuously over days 1-4, vinorelbine tartrate IV over 6-10 minutes on days 1 and 5, and bortezomib intravenously on days 1, 4, and 8, and filgrastim (G-CSF) by vein or subcutaneously beginning on day 6 and continuing until blood counts recover or peripheral blood stem cells (PBSC) are harvested. Treatment cycles repeat every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bortezomib (Velcade, PS-341) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Dec 31, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor therapy, chemotherapy) Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.

Drug: ifosfamide; Given IV; Other Names: Cyfos Holoxan IFF IFX IPP ; Drug: bortezomib; Given IV; Other Names: LDP 341 MLN341 VELCADE ; Drug: vinorelbine tartrate; Given IV; Other Names: Eunades navelbine ditartrate NVB VNB ; Biological: filgrastim; Given IV or SC; Other Names: G-CSF Neupogen

Outcome Measures

Primary Outcome Measures

1. Complete Response (CR) [After 2 cycles of treatment]

   CR is defined as at least 80% reduction in the sum of the products of the perpendicular diameters of each of the nodal masses or return to normal size, along with negative nuclear medicine imaging.

Secondary Outcome Measures

1. Number of Participants With Grade 3 or 4 Toxicity [4 weeks following completion of therapy]

   Grade 3 and 4 non-hematologic toxicity during protocol therapy. The number of patients that experience CTC Version 4 grade 3 or higher non-hematologic at any time during protocol therapy

2. Overall Response Rate [After 2 cycles and 4 cycles]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

3. Induction Success Rate [After 2 cycles and 4 cycles]

   Induction success is defined as achieving CR or PR without a targeted primary toxicity. Primary toxicity includes toxic death (which is any death predominantly attributable to treatment-related toxicities or complications, occurring during or within one month of the completion of therapy), Non-hematologic grades 3 or 4 toxicities attributable to drug (with the specific exclusion of 1) Grade 3 or 4 nausea or vomiting, 2) grade 3 transaminases (AST/ALT) elevations which return to < grade 1 prior to the time of the next treatment course, 3) grade 3 or 4 fever or infection, and 4) Grade 3 mucositis.) and Hematologic toxicity (Delay of >2 weeks in the start of re-induction cycle 2 or in hematologic recovery after cycle 2 secondary to severe myelosuppression, infection, or sepsis.)

4. Rate of Successful PBSC Harvest [After 2 cycles]

   Success is defined as the ability to harvest 2x10^6 CD34+ cells/kg within 5 collection days.

5. Biological Markers [Before, during, and after treatment]

   Assessing baseline NF-kB protein levels in tumor tissue

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 29 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed Hodgkin's lymphoma at time of relapse or disease progression, meeting all of the following criteria:

• Stage I-IV disease

• No morphologically unclassifiable disease

• Meets 1 of the following criteria:

• Mixed cellularity

• Lymphocytic depletion (LD)

• LD, diffuse fibrosis

• LD, reticular

• Lymphocyte predominance (LP)

• LP, diffuse

• LP, nodular

• Nodular sclerosis (NS)

• NS, cellular phase

• NS, lymphocytic predominance

• NS, mixed cellularity

• NS, LD

• Not otherwise specified

• Primary refractory disease OR disease in first relapse, except for the following:

• Patients who achieved a complete response after treatment on protocol COG-AHOD0431 who experience a biopsy-proven recurrence after doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide without involved-field radiotherapy

• Patients on the observation-only arm of protocol COG-AHOD0431

• Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or kidney)

• Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or thrombocytopenia are allowed provided both of the following criteria are met:

• Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)

• Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)

• Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy PS 60-100% (for patients =< 16 years of age)

• Life expectancy >= 2 months

• Absolute neutrophil count >= 1,000/mm^3

• Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone marrow involvement)

• Creatinine =< 1.5 times upper limit of normal (ULN)

• Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2

• AST and ALT =< 2.5 times ULN

• Bilirubin =< 1.5 times ULN

• Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide study

• Patients with a seizure disorder are eligible if on a nonenzyme-inducing anticonvulsant and seizures are well controlled

• No CNS toxicity > grade 2

• No serious intercurrent illnesses

• No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any component of the study drugs

• No peripheral neuropathy > grade 1

• No known hypersensitivity to bortezomib, boron, or mannitol

• No other concurrent chemotherapy or immunomodulating agents (including steroids)

• Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic reactions

• No dexamethasone or aprepitant as an antiemetic

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Recovered from prior therapy

• No prior bortezomib or other proteasome inhibitors

• At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)

• More than 14 days since prior investigational drugs

• No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including phenytoin, carbamazepine, phenobarbital, or other anticonvulsants

• Benzodiazepine or gabapentin allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Oncology Group	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Terzah Horton, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00381940
• Other Study ID Numbers: NCI-2009-01063; NCI-2009-01063; CDR0000500142; AHOD0521; AHOD0521; U10CA098543; NCT01648439
• First Posted: Sep 28, 2006
• Last Update Posted: Mar 24, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Recurrence; Sclerosis; Bortezomib; Vinorelbine; Ifosfamide

Study Results

Participant Flow

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Period Title: Overall Study
STARTED	26
COMPLETED	21
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Overall Participants	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.9 (2.6)
Age (Count of Participants)
<=18 years	23 88.5%
Between 18 and 65 years	3 11.5%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 46.2%
Male	14 53.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 7.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 15.4%
White	18 69.2%
More than one race	0 0%
Unknown or Not Reported	2 7.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 15.4%
Not Hispanic or Latino	22 84.6%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	23 88.5%
Australia	1 3.8%
Canada	2 7.7%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR)
Description	CR is defined as at least 80% reduction in the sum of the products of the perpendicular diameters of each of the nodal masses or return to normal size, along with negative nuclear medicine imaging.
Time Frame	After 2 cycles of treatment

Outcome Measure Data

Analysis Population Description

Analysis population includes all patients evaluable for tumor response. Three enrolled patients are excluded: 1 ineligible, 1 who was removed from treatment after 1 dose of bortezomib, and 1 who received only 1/3 dose of bortezomib in cycle 1 and part of cycle 2 due to pharmacy error.

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	23
With CR	2 7.7%
Without CR	21 80.8%

2. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Toxicity
Description	Grade 3 and 4 non-hematologic toxicity during protocol therapy. The number of patients that experience CTC Version 4 grade 3 or higher non-hematologic at any time during protocol therapy
Time Frame	4 weeks following completion of therapy

Outcome Measure Data

Analysis Population Description

25 patients reported, 1 ineligible patient not included in adverse events.

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	25
Count of Participants [Participants]	9 34.6%

3. Secondary Outcome

Title	Overall Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	After 2 cycles and 4 cycles

Outcome Measure Data

Analysis Population Description

There were 23 patients evaluable after 2 cycles and 12 patients evaluable after 4 cycles. 1 patient was excluded after cycle 2 and cycle 4 due to pharmacy error. 2 patients were excluded after cycle 2 due to ineligibility and removal from treatment after 1 dose of bortezomib.

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	23
Overall Response Rate (After 2 cycles)	19 73.1%
Overall Response Rate (After 4 cycles)	12 46.2%

4. Secondary Outcome

Title	Induction Success Rate
Description	Induction success is defined as achieving CR or PR without a targeted primary toxicity. Primary toxicity includes toxic death (which is any death predominantly attributable to treatment-related toxicities or complications, occurring during or within one month of the completion of therapy), Non-hematologic grades 3 or 4 toxicities attributable to drug (with the specific exclusion of 1) Grade 3 or 4 nausea or vomiting, 2) grade 3 transaminases (AST/ALT) elevations which return to < grade 1 prior to the time of the next treatment course, 3) grade 3 or 4 fever or infection, and 4) Grade 3 mucositis.) and Hematologic toxicity (Delay of >2 weeks in the start of re-induction cycle 2 or in hematologic recovery after cycle 2 secondary to severe myelosuppression, infection, or sepsis.)
Time Frame	After 2 cycles and 4 cycles

Outcome Measure Data

Analysis Population Description

There were 23 patients evaluable after 2 cycles and 12 patients evaluable after 4 cycles. 1 patient was excluded after cycle 2 and cycle 4 due to pharmacy error. 2 patients were excluded after cycle 2 due to ineligibility and removal from treatment after 1 dose of bortezomib.

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	23
Induction Success Rate (After 2 cycles)	19 73.1%
Induction Success Rate (After 4 cycles)	12 46.2%

5. Secondary Outcome

Title	Rate of Successful PBSC Harvest
Description	Success is defined as the ability to harvest 2x10^6 CD34+ cells/kg within 5 collection days.
Time Frame	After 2 cycles

Outcome Measure Data

Analysis Population Description

Analysis population includes all patients evaluable after cycle 2. Six enrolled patients are excluded: 1 ineligible, 1 who was removed from treatment after 1 dose of bortezomib, and 1 who received only 1/3 dose of bortezomib in cycle 1 and part of cycle 2 due to pharmacy error, 3 who did not have recorded data

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	20
Count of Participants [Participants]	19 73.1%

6. Secondary Outcome

Title	Biological Markers
Description	Assessing baseline NF-kB protein levels in tumor tissue
Time Frame	Before, during, and after treatment

Outcome Measure Data

Analysis Population Description

Corresponding data were not collected

Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	25 patients reported, 1 ineligible patient not included in adverse events.
Arm/Group Title	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
Arm/Group Description	This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment cycle repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy. ifosfamide: Given IV bortezomib: Given IV vinorelbine ditartrate: Given IV filgrastim: Given IV or SC
All Cause Mortality
	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
	Affected / at Risk (%)	# Events
Total	4/25 (16%)
Gastrointestinal disorders
Abdominal pain	1/25 (4%)	1
Nausea	1/25 (4%)	1
Vomiting	1/25 (4%)	1
General disorders
Fatigue	1/25 (4%)	1
Immune system disorders
Anaphylaxis	1/25 (4%)	1
Metabolism and nutrition disorders
Anorexia	1/25 (4%)	1
Dehydration	1/25 (4%)	1
Hypokalemia	2/25 (8%)	2
Nervous system disorders
Depressed level of consciousness	1/25 (4%)	1
Neuralgia	1/25 (4%)	1
Psychiatric disorders
Depression	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Ifosfamide, Vinorelbine, Bortezomib)
	Affected / at Risk (%)	# Events
Total	18/25 (72%)
Blood and lymphatic system disorders
Anemia	4/25 (16%)	4
Febrile neutropenia	3/25 (12%)	3
Gastrointestinal disorders
Abdominal pain	1/25 (4%)	1
Mucositis oral	1/25 (4%)	1
Vomiting	1/25 (4%)	1
General disorders
Death NOS	3/25 (12%)	3
Infections and infestations
Catheter related infection	2/25 (8%)	2
Infections and infestations - Other, specify	7/25 (28%)	7
Urinary tract infection	1/25 (4%)	1
Injury, poisoning and procedural complications
Vascular access complication	1/25 (4%)	1
Investigations
Activated partial thromboplastin time prolonged	1/25 (4%)	1
Alanine aminotransferase increased	2/25 (8%)	2
Blood bilirubin increased	1/25 (4%)	1
Lymphocyte count decreased	4/25 (16%)	4
Neutrophil count decreased	6/25 (24%)	6
Platelet count decreased	3/25 (12%)	3
White blood cell decreased	5/25 (20%)	5
Metabolism and nutrition disorders
Anorexia	1/25 (4%)	1
Hyperglycemia	2/25 (8%)	2
Hyperkalemia	1/25 (4%)	1
Hypermagnesemia	1/25 (4%)	1
Hypocalcemia	1/25 (4%)	1
Hypokalemia	3/25 (12%)	3
Hypophosphatemia	2/25 (8%)	2
Musculoskeletal and connective tissue disorders
Bone pain	2/25 (8%)	2
Nervous system disorders
Neuralgia	1/25 (4%)	1
Peripheral motor neuropathy	1/25 (4%)	1
Peripheral sensory neuropathy	2/25 (8%)	2
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.