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Adult Lymphocyte Depletion Hodgkin LymphomaPhase 2NCT00381940

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

A Phase 2 study testing ifosfamide, bortezomib and vinorelbine tartrate in people with Adult Lymphocyte Depletion Hodgkin Lymphoma and Adult Lymphocyte Predominant Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 29 years
What is being tested?
ifosfamide, bortezomib and vinorelbine tartrate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Jan 2007to 31 Dec 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 51Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Oncology Group

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

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.

Read the 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.

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:

  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.

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.

Being tested
ifosfamide, bortezomib, vinorelbine tartrate, filgrastim
Medical subject headings
Hodgkin Disease, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ifosfamideDrug

    Also called Cyfos, Holoxan, IFF, IFX

    Given IV

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • vinorelbine tartrateDrug

    Also called Eunades, navelbine ditartrate, NVB, VNB

    Given IV

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given IV or SC

Study groups in NCT00381940
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy, chemotherapy)ExperimentalPatients 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.
Receives: Drug: ifosfamide; Drug: bortezomib; Drug: vinorelbine tartrate; Biological: filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response (CR)

    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.

    Measured: After 2 cycles of treatment

Secondary outcomes (5)

  1. Number of Participants With Grade 3 or 4 Toxicity

    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

    Measured: 4 weeks following completion of therapy

  2. Overall Response Rate

    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

    Measured: After 2 cycles and 4 cycles

  3. Induction Success Rate

    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.)

    Measured: After 2 cycles and 4 cycles

  4. Rate of Successful PBSC Harvest

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

    Measured: After 2 cycles

  5. Biological Markers

    Assessing baseline NF-kB protein levels in tumor tissue

    Measured: Before, during, and after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2006 (estimated)
  2. Study startJan 2007
  3. Primary completionJun 2008
  4. Study completion31 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381940
Sponsor's protocol ID
NCI-2009-01063
Other IDs
NCI-2009-01063, CDR0000500142, AHOD0521, AHOD0521, U10CA098543
Status last verified
Mar 2021
First submitted
26 Sep 2006
Last updated
24 Mar 2021

Publications

  • 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.

    PubMed 25833390

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ifosfamide, bortezomib and vinorelbine tartrate in people with Adult Lymphocyte Depletion Hodgkin Lymphoma and Adult Lymphocyte Predominant Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) (time frame: After 2 cycles of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00381940, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.

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