Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy
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Purpose
This phase II trial is studying the side effects and how well giving bortezomib together with ifosfamide and vinorelbine works in treating young patients with Hodgkin's lymphoma that is recurrent or did not respond to previous therapy. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as ifosfamide and vinorelbine tartrate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may help ifosfamide and vinorelbine work better by making cancer cells more sensitive to the drugs. Giving bortezomib together with ifosfamide and vinorelbine tartrate may kill more cancer cells
| Condition | Intervention | 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 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Bortezomib (Velcade, PS-341, IND #58443) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease |
- Comparison of complete response between IVB and historical controls of IV after 2 courses [ Time Frame: At 42 days ] [ Designated as safety issue: No ]Compared using a two sample test for proportions. 95% confidence interval will be calculated.
- Comparison of complete response rate between IVB and historical controls of IV after 4 courses [ Time Frame: At 84 days ] [ Designated as safety issue: No ]Compared using a two sample test for proportions. 95% confidence interval will be calculated.
- Toxic death, any death predominantly attributable to treatment-related toxicities or complications [ Time Frame: Up to 1 month after completion of therapy ] [ Designated as safety issue: Yes ]Graded using the National Cancer Institute (NCI) Common Terminology Criteria version 4.0.
- Non-hematologic grades 3 or 4 toxicities attributable to drug [ Time Frame: 4 weeks following the completion of re-induction therapy ] [ Designated as safety issue: Yes ]Graded using the NCI Common Terminology Criteria version 4.0.
- Overall response (CR + PR) [ Time Frame: After 2 courses of IVB, at 42 days ] [ Designated as safety issue: No ]95% confidence interval will be calculated.
- Overall response (CR + PR) [ Time Frame: After 4 courses of IVB, at 84 days ] [ Designated as safety issue: No ]95% confidence intervals will be calculated.
- Rate of successful PBSC harvest during re-induction [ Time Frame: Following course 2, at 42 days ] [ Designated as safety issue: No ]The proportion of patients who are able to mobilize sufficient hematopoietic stem cells will be calculated, along with the 95% exact confidence interval.
| Enrollment: | 48 |
| Study Start Date: | January 2007 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Drug: bortezomib
Given IV
Other Names:
Drug: vinorelbine tartrate
Given IV
Other Names:
Biological: filgrastim
Given IV or SC
Other Names:
|
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 response rate in patients treated with bortezomib, ifosfamide, and vinorelbine ditartrate (vinorelbine tartrate) (IVB) and compare it 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, 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 peripheral blood stem cells (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.
After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.
Eligibility| Ages Eligible for Study: | up to 29 Years |
| Genders Eligible for Study: | Both |
| 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 achieving 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 More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00381940 History of Changes |
| Obsolete Identifiers: | NCT01648439 |
| Other Study ID Numbers: | NCI-2009-01063, AHOD0521, U10CA098543 |
| Study First Received: | September 26, 2006 |
| Last Updated: | October 30, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hodgkin Disease Lymphoma Sclerosis Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Pathologic Processes Ifosfamide Isophosphamide mustard Vinorelbine Bortezomib Vinblastine |
Lenograstim Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Protease Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013