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

NCT ID: NCT00381940

Last Updated: 2021-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2016-12-31

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.

Detailed Description

PRIMARY OBJECTIVES:

I. 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.

II. 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:

I. 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.

II. 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ifosfamide

Intervention Type: DRUG

Given IV

bortezomib

Intervention Type: DRUG

Given IV

vinorelbine tartrate

Intervention Type: DRUG

Given IV

filgrastim

Intervention Type: BIOLOGICAL

Given IV or SC

Interventions

ifosfamide

Given IV

Intervention Type: DRUG

bortezomib

Given IV

Intervention Type: DRUG

vinorelbine tartrate

Given IV

Intervention Type: DRUG

filgrastim

Given IV or SC

Intervention Type: BIOLOGICAL

Other Intervention Names

Cyfos; Holoxan; IFF; IFX; IPP; LDP 341; MLN341; VELCADE; Eunades; navelbine ditartrate; NVB; VNB; G-CSF; Neupogen

Eligibility Criteria

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

• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Terzah Horton

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Philadelphia, Pennsylvania, United States

Countries

United States

References

Horton TM, Drachtman RA, Chen L, Cole PD, McCarten K, Voss S, Guillerman RP, Buxton A, Howard SC, Hogan SM, Sheehan AM, Lopez-Terrada D, Mrazek MD, Agrawal N, Wu MF, Liu H, De Alarcon PA, Trippet TM, Schwartz CL. A phase 2 study of bortezomib in combination with ifosfamide/vinorelbine in paediatric patients and young adults with refractory/recurrent Hodgkin lymphoma: a Children's Oncology Group study. Br J Haematol. 2015 Jul;170(1):118-22. doi: 10.1111/bjh.13388. Epub 2015 Apr 1.

Reference Type: DERIVED

PMID: 25833390 (View on PubMed)

Other Identifiers

NCI-2009-01063

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000500142

Identifier Type: -

Identifier Source: secondary_id

AHOD0521

Identifier Type: OTHER

Identifier Source: secondary_id

AHOD0521

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01063

Identifier Type: -

Identifier Source: org_study_id

NCT01648439

Identifier Type: -

Identifier Source: nct_alias