Trial Outcomes & Findings for Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy (NCT NCT00381940)

NCT ID: NCT00381940

Last Updated: 2021-03-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

After 2 cycles of treatment

Results posted on

2021-03-24

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) 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 Study STARTED	26
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) 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 Study Lack of Efficacy	3
Overall Study Protocol Violation	1
Overall Study Ineligible	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=26 Participants 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
Age, Continuous	15.9 years STANDARD_DEVIATION 2.6 • n=5 Participants
Age, Categorical <=18 years	23 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants
Region of Enrollment Australia	1 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants

PRIMARY outcome

Timeframe: After 2 cycles of treatment

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=23 Participants 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
Complete Response (CR) With CR	2 participants
Complete Response (CR) Without CR	21 participants

SECONDARY outcome

Timeframe: 4 weeks following completion of therapy

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

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

Outcome measures

Outcome measures
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=25 Participants 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
Number of Participants With Grade 3 or 4 Toxicity	9 Participants

SECONDARY outcome

Timeframe: After 2 cycles and 4 cycles

Population: 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.

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

Outcome measures

Outcome measures
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=23 Participants 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 Response Rate Overall Response Rate (After 2 cycles)	19 Participants
Overall Response Rate Overall Response Rate (After 4 cycles)	12 Participants

SECONDARY outcome

Timeframe: 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.)

Outcome measures

Outcome measures
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=23 Participants 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
Induction Success Rate Induction Success Rate (After 2 cycles)	19 Participants
Induction Success Rate Induction Success Rate (After 4 cycles)	12 Participants

SECONDARY outcome

Timeframe: After 2 cycles

Population: 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

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

Outcome measures

Outcome measures
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=20 Participants 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
Rate of Successful PBSC Harvest	19 Participants

SECONDARY outcome

Timeframe: Before, during, and after treatment

Population: Corresponding data were not collected

Assessing baseline NF-kB protein levels in tumor tissue

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Ifosfamide, Vinorelbine, Bortezomib)

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=25 participants at risk 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
Gastrointestinal disorders Abdominal pain	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Gastrointestinal disorders Nausea	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Gastrointestinal disorders Vomiting	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
General disorders Fatigue	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Immune system disorders Anaphylaxis	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Anorexia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Dehydration	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hypokalemia	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Nervous system disorders Depressed level of consciousness	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Nervous system disorders Neuralgia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Psychiatric disorders Depression	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.

Other adverse events

Other adverse events
Measure	Treatment (Ifosfamide, Vinorelbine, Bortezomib) n=25 participants at risk 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
Blood and lymphatic system disorders Anemia	16.0% 4/25 • Number of events 4 25 patients reported, 1 ineligible patient not included in adverse events.
Blood and lymphatic system disorders Febrile neutropenia	12.0% 3/25 • Number of events 3 25 patients reported, 1 ineligible patient not included in adverse events.
Gastrointestinal disorders Abdominal pain	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Gastrointestinal disorders Mucositis oral	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Gastrointestinal disorders Vomiting	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
General disorders Death NOS	12.0% 3/25 • Number of events 3 25 patients reported, 1 ineligible patient not included in adverse events.
Infections and infestations Catheter related infection	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Infections and infestations Infections and infestations - Other, specify	28.0% 7/25 • Number of events 7 25 patients reported, 1 ineligible patient not included in adverse events.
Infections and infestations Urinary tract infection	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Injury, poisoning and procedural complications Vascular access complication	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Activated partial thromboplastin time prolonged	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Alanine aminotransferase increased	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Blood bilirubin increased	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Lymphocyte count decreased	16.0% 4/25 • Number of events 4 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Neutrophil count decreased	24.0% 6/25 • Number of events 6 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations Platelet count decreased	12.0% 3/25 • Number of events 3 25 patients reported, 1 ineligible patient not included in adverse events.
Investigations White blood cell decreased	20.0% 5/25 • Number of events 5 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Anorexia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hyperglycemia	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hyperkalemia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hypermagnesemia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hypocalcemia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hypokalemia	12.0% 3/25 • Number of events 3 25 patients reported, 1 ineligible patient not included in adverse events.
Metabolism and nutrition disorders Hypophosphatemia	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Musculoskeletal and connective tissue disorders Bone pain	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Nervous system disorders Neuralgia	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Nervous system disorders Peripheral motor neuropathy	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.
Nervous system disorders Peripheral sensory neuropathy	8.0% 2/25 • Number of events 2 25 patients reported, 1 ineligible patient not included in adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	4.0% 1/25 • Number of events 1 25 patients reported, 1 ineligible patient not included in adverse events.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0567

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60