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Trial of VELCADE and Rituxan as Front-line Tx for Low-grade NHL

26 augustus 2019 bijgewerkt door: Northwestern University

A Phase II Trial of Combination Bortezomib and Rituximab as Front-line Therapy for Low-grade Non-Hodgkin's Lymphoma

Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.

This phase II trial is studying how well giving bortezomib together with rituximab works as first-line therapy in treating patients with low-grade B-cell non-Hodgkin's lymphoma.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This is a multicenter, prospective study.

  • Induction therapy: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 of all subsequent courses. Treatment repeats every 35 days for 3 courses. Patients achieving a complete response, partial response, or stable disease proceed to maintenance therapy.
  • Maintenance therapy: Beginning 6-8 weeks after induction therapy, patients receive bortezomib IV over 3-5 seconds and rituximab IV on day 1. Treatment repeats every 60 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline and periodically during study treatment.

After completion of study therapy, patients are followed every 3 months for 2 years.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

42

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Florida
      • Miami, Florida, Verenigde Staten, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern University
      • Chicago, Illinois, Verenigde Staten, 60611-2998
        • Hematology-Oncology Associates of Illinois
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten, 19111-2497
        • Fox Chase Cancer Center - Philadelphia

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Histologically confirmed low-grade B-lymphocyte non-Hodgkins lymphoma
  • Life expectancy > 12 months

Exclusion Criteria:

  • No known history of HIV infection
  • No other active infection
  • No peripheral neuropathy ≥ grade 2 within the past 14 days
  • No uncontrolled hypertension

  • None of the following cardiac conditions:

    • Myocardial infarction within the past 6 months
    • No heart failure
    • Uncontrolled angina
    • Severe uncontrolled ventricular arrhythmias
    • Electrocardiographic evidence of acute ischemia
    • Active conduction system abnormalities
  • No serious medical or psychiatric illness that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior therapy for non-Hodgkins lymphoma
  • No prior bortezomib or rituximab
  • At least 3 weeks since prior chemotherapy, radiation therapy, immunotherapy, systemic anticancer biologic therapy, or anticancer hormonal therapy
  • At least 2 weeks since prior investigational drugs
  • No other concurrent systemic cytotoxic chemotherapy or investigational agents + No leukemia

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Bortezomib and Rituximab
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Geneesmiddel: Rituximab
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Andere namen:
  • Rituxan
Geneesmiddel: bortezomib
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Andere namen:
  • Velcade, PS-341

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Response Rate (Complete Response and Partial Response) After Three Inductions Cycles of Treatment.
Tijdsspanne: At baseline and at the completion of 3 cycles of treatment where 1 cycle equals 35 days.

The primary objective of this study is to assess the overall response rate. Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 3 cycles of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.
At baseline and at the completion of 3 cycles of treatment where 1 cycle equals 35 days.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Response Rate After 1 Course of Induction Therapy
Tijdsspanne: At baseline and at the completion of cycle 1 (1 cycle =35 days)

Overall response rate (ORR) after 1 cycle of bortezomib/rituximab induction therapy.

Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 1 cycle of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.
At baseline and at the completion of cycle 1 (1 cycle =35 days)
Overall Response Rate After Completion of Maintenance Therapy
Tijdsspanne: At baseline and every 2 months during treatment of up to 3 cycles of induction (1 cycle =35days) and 4 cycles of maintenance (1 cycle =2 months) for up to 12 months.

Overall response rate at completion of bortezomib/rituximab maintenance therapy.

Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 3 cycles of bortezomib/rituximab induction therapy and up to 4 cycles of maintenance for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.
At baseline and every 2 months during treatment of up to 3 cycles of induction (1 cycle =35days) and 4 cycles of maintenance (1 cycle =2 months) for up to 12 months.
Duration of Overall Response
Tijdsspanne: Every 2 months for up to 12 months then every 6 months for 2 years and annually for 1 year

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded)until the first date that recurrent or progressive disease is objectively documented.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Progressive disease (PD) requires the appearance of any new lesion or increase by > 50% in the size of previously involved sites.
Every 2 months for up to 12 months then every 6 months for 2 years and annually for 1 year
Number of Patients That Experience Adverse Events With Bortezomib/Rituximab Combination Treatment
Tijdsspanne: Day 1 of each cycle and at the completion of cycles 1 and 3, during treatment up to 12 months

Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy. Data will be collected for grade 3 and grade 4 adverse events experienced by patients that are determined to be at least possibly related to at least one study drug. Toxicity data for bortezomib/rituximab will be collected on day 1 of every cycle (1 cycle = 35 days) for up to 7 cycles during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Day 1 of each cycle and at the completion of cycles 1 and 3, during treatment up to 12 months
Tissue Evaluation
Tijdsspanne: At baseline and at response assessment 1 after induction part A, 2, after induction part B and 3, maintenance period.
Tissue microarray analysis from paraffin embedded tissue, gene expression profiling from frozen tissue (both from initial node biopsy collected/stored) and whole blood analysis of FCγR polymorphism
At baseline and at response assessment 1 after induction part A, 2, after induction part B and 3, maintenance period.
Correlation of Tumor Burden
Tijdsspanne: At the start of treatment and at Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS and OS for all patients is reported at 4 years.

Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index. All patients enrolled in the study were required to have high tumor burden (HTB) as defined by GELF, where HTB is defined as representing higher risk disease and poorer outcomes than low tumor burden (LTB). Patients were put into low risk or high risk FLIPI groups. Low risk group with a score of 0-2 and high risk group with a score of 3-5.

A FLIPI score of 0 to 1 = "low risk" with a 10 year overall survival of 70%. A score of 2= "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%. Data was collected in connection with high or low risk FLIPI and Progression Free Survival (PFS) or Overall Survival (OS) and is reported as percentage patient with high/low risk that are progression free or alive.
At the start of treatment and at Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS and OS for all patients is reported at 4 years.
Percentage of Patients With Treatment Failure
Tijdsspanne: Median follow up for all patients was 50 months and on intent to treat, TTF rate for all patients is reported at 4 years.
Time to Treatment Failure (TTF) rate measured, from the time of first treatment to disease progression, relapse, second tumor, death from any cause, treatment toxicity requiring termination from the study, or for any reason treatment is discontinued permanently.
Median follow up for all patients was 50 months and on intent to treat, TTF rate for all patients is reported at 4 years.
Progression Free Survival (PFS) Rate
Tijdsspanne: Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS for all patients is reported at 4 years.

Progression Free Survival is measured from the time of first induction infusion to disease progression, relapse, second tumor, or death from any cause.

Progressive disease (PD) requires the following:

  1. Appearance of any new lesion or increase by > 50% in the size of previously involved sites.
  2. Increase of > 50% in the SPD from nadir measurement of all involved dominant lymph nodes and liver nodules and spleen nodules or unequivocal progression in any non measurable disease or nondominant site.
  3. > 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node
Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS for all patients is reported at 4 years.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Northwestern University

Medewerkers

Robert H. Lurie Cancer Center

Onderzoekers

  • Hoofdonderzoeker: Andrew M. Evens, DO, MS, Northwestern University

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

9 augustus 2006

Primaire voltooiing (Werkelijk)

22 mei 2012

Studie voltooiing (Werkelijk)

10 oktober 2014

Studieregistratiedata

Eerst ingediend

24 augustus 2006

Eerst ingediend dat voldeed aan de QC-criteria

24 augustus 2006

Eerst geplaatst (Schatting)

29 augustus 2006

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 september 2019

Laatste update ingediend die voldeed aan QC-criteria

26 augustus 2019

Laatst geverifieerd

1 oktober 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NU 06H1
  • STU00005335 (Andere identificatie: Northwestern University IRB)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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