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Recurrent Diffuse Large B-Cell LymphomaPhase 3SPINOZANCT02366663

BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL

A Phase 3 study testing 90-Yttrium Ibritumomab tiuxetan, Carmustine and Etoposide in people with Recurrent Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized phase III trial studies 90-yttrium ibritumomab tiuxetan and combination chemotherapy compared with combination chemotherapy alone before stem cell transplant in treating patients with diffuse large b-cell non-Hodgkin lymphoma that has returned after a period of improvement. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
90-Yttrium Ibritumomab tiuxetan, Carmustine and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesUnited States
Study dates
Jan 2015to Oct 2016
Phase
Phase 3
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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.
  • Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.
  • Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.
  • Patients with adequate autologous stem cell collection for transplantation (target >= 2.5 x 10^6 CD34+ cells/kg).
  • Patients must sign written informed consent.
  • Adequate birth control in fertile patients.
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  • All prior chemotherapy completed at least three weeks before study treatment.
  • Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).
  • Negative HIV antibody.

Who cannot join

  • Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.
  • Two or more relapses after initial response to induction chemotherapy.
  • High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent to all other selection criteria.
  • Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit.
  • Creatinine > 2.0 mg/dl.
  • KPS < 70.
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  • Uncontrolled infection.
  • Pregnancy or lactation.
  • Abnormal lung diffusion capacity (DLCO < 40% predicted).
  • Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2.
  • Active CNS disease involvement.
  • Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy > 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
  • Pleural effusion or ascites > 1 liter.
  • Known hypersensitivity to rituximab.
  • Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.
  • Prior radioimmunotherapy.
  • Prior autologous or allogeneic HSCT.
  • Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.
  • Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume.
  • Patients who have received >500cGy radiation to the kidneys will be excluded from the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • City of Hope Medical Center

    Duarte, California, 91010

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring ASCT for Relapsed DLBCL

This randomized phase III trial studies 90-yttrium ibritumomab tiuxetan and combination chemotherapy compared with combination chemotherapy alone before stem cell transplant in treating patients with diffuse large b-cell non-Hodgkin lymphoma that has returned after a period of improvement. Radioactive substances linked to monoclonal antibodies, such as 90-yttrium ibritumomab tiuxetan, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, etoposide phosphate, cytarabine, and melphalan (BEAM), work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether 90-yttrium ibritumomab tiuxetan and BEAM before a stem cell transplant are more effective than BEAM alone in treating patients with diffuse large b-cell non-Hodgkin lymphoma.

Read the detailed description

PRIMARY OBJECTIVES: I. To compare overall survival (OS) between the two transplant arms, with at least a two year of follow-up. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS), complete response (CR) and partial response (PR) proportion at day 100, time to hematopoietic recovery, incidence of infection, grade III-IV toxicities, treatment-related mortality, incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).

OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive rituximab intravenously (IV) on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours twice daily (BID) on days -5 to -2; etoposide IV over 1 hour BID or once daily (QD) on days -5 to -2; and melphalan IV on day -1. Patients then undergo peripheral blood stem cell (PBSC) transplant on day 0. ARM II: Patients receive BEAM as in Arm I and undergo PBSC transplant on day 0.

After completion of study treatment, patients are followed up weekly for 30 days, 100 days, 6 months, 1 year, every 3 months for 1 year, and then annually for 3 years.

Being tested
90-Yttrium Ibritumomab tiuxetan, Carmustine, Etoposide, Cytarabine, Melphalan
Keywords
Non-Hodgkin's lymphoma, autologous stem cell transplantation, radioimmunotherapy, Zevalin, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Immune System Diseases, Immunoproliferative Disorders, Lymphatic Diseases, Lymphoma, B-Cell, Lymphoproliferative Disorders, Neoplasms, Neoplasms by Histologic Type, Antibodies, Monoclonal, Immunologic Factors, Pharmacologic Actions, Physiological Effects of Drugs
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Immune System Diseases, Immunoproliferative Disorders, Lymphatic Diseases, Lymphoma, B-Cell, Lymphoproliferative Disorders

What participants receive

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

  • 90-Yttrium Ibritumomab tiuxetanRadiation

    Also called IDEC Y2B8, Zevalin

    0.4 mCi/kg given IV

  • CarmustineDrug

    Also called BiCNU, FDA 0345

    Given IV

  • EtoposideDrug

    Also called VP-16, Lastet

    Given IV

  • CytarabineDrug

    Also called Cytosar-U, CHX-3311, U-19920

    Given IV

  • MelphalanDrug

    Also called Alkeran

    Given IV

  • Autologous Hematopoietic Stem Cell TransplantProcedure or surgery

    Also called Autologous Stem Cell Transplant

    Autologous Hematopoietic Stem Cell Transplantation (ASCT)

  • RituximabBiological

    Also called MOAB IDEC-C2B8

    Given IV

Study groups in NCT02366663
Study groupRoleWhat they receive
Arm I (ZBEAM)ExperimentalPatients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
Receives: Radiation: 90-Yttrium Ibritumomab tiuxetan; Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Procedure: Autologous Hematopoietic Stem Cell Transplant; Biological: Rituximab
Arm II (BEAM)Active comparatorPatients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
Receives: Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Procedure: Autologous Hematopoietic Stem Cell Transplant

What is being measured

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

  1. Overall Survival

    Survival estimates will be calculated using the Kaplan-Meier method

    Measured: Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization

Secondary outcomes (10)

  1. Progression-free Survival

    Survival estimates will be calculated using the Kaplan-Meier method

    Measured: Measured from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up whichever comes first, for up to 5 years post randomization

  2. Time to Progression

    Time-to-event will be measured from the date of ASCT.

    Measured: Up to 5 years

  3. Number of Patients With Complete or Partial Response at Day 30

    Definition of disease status is based on the article of Revised Response Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al, 2007). Tests used for evaluation of disease status would be physical examination, laboratory testing, bone marrow testing, bone marrow biopsy and aspirate, PET scan, and CT scans of neck, chest, abdomen and pelvis as indicated.

    Measured: Day 0 to Day +30 post-HCT

  4. Time to Neutrophil Engraftment

    Time to neutrophil engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated.

    Measured: Day 0 to Day 100 post-HCT

  5. Incidence of Infection

    Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient. The proportion of patients developing infections will be compared between treatment arms.

    Measured: Day 0 to Day +100 post-HCT

  6. Incidence of Non-relapse Mortality (NRM) Defined as Death Occurring in a Patient From Causes Other Than Relapse or Progression

    The cumulative incidence of NRM will be estimated using the method described by Gooley et al. Differences between cumulative incidence curves in the presence of a competing risk will be tested using the Gray method.

    Measured: From randomization until non-disease related death, or last follow-up, whichever comes first, assessed up to 5 years

  7. Cumulative Incidence of Secondary Malignancies

    Incidence of myelodysplastic syndrome (MDS), and secondary acute Myelogenous leukemia (AML) will be compared between the treatment arms using Gray's test.

    Measured: Up to 5 years

  8. Time to Platelet Engraftment

    Time to platelet engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated.

    Measured: Day 0 to Day 100 post-HCT

  9. Number of Patients With Grade 3-5 Toxicities Graded by the NCI CTCAE Version 4.0

    Observed toxicities will be summarized in terms of type and severity. In accordance with the secondary study objectives, descriptive analyses on these data will be performed.

    Measured: Day -21 to Day +100 post-HCT

  10. Cumulative Incidence of New, Abnormal Cytogenetics

    The cumulative incidence of therapy related new, abnormal cytogenetics will be estimated for both groups taking into account the competing risk of death among patients who do not develop a second malignancy.

    Measured: Day 0 to Year 5 post-HCT

Timeline

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

  1. First posted19 Feb 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionOct 2016
  4. Study completionOct 2016

Why it stopped: Withdrawal of sponsor support

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02366663
Sponsor's protocol ID
12338
Other IDs
NCI-2015-00185
Acronym
SPINOZA
Status last verified
Feb 2018
First submitted
9 Feb 2015
Last updated
12 Mar 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 90-Yttrium Ibritumomab tiuxetan, Carmustine and Etoposide in people with Recurrent Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by City of Hope Medical Center at 2 sites 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 9 inclusion and 20 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: stopped early, as of the sponsor's last update on 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 13 Feb 2018). 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?

Overall Survival (time frame: Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization). 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 NCT02366663.

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 12 Mar 2018.

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