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AzTrials

LymphomaPhase 1NCT00392691

Melphalan, Yttrium Y 90 Ibritumomab Tiuxetan, and Rituximab Followed by Autologous Stem Cell Transplant in Treating Older Patients With Non-Hodgkin's Lymphoma That Has Relapsed or Not Responded to Previous Treatment

A Phase 1 study testing ibritumomab tiuxetan, rituximab and melphalan in people with Lymphoma, run by Swiss Cancer Institute at 10 sites in Switzerland.

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

RATIONALE: Giving chemotherapy drugs, such as melphalan, before an autologous stem cell transplant helps stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 65 to 120 years
Conditions the study is for
Lymphoma
What is being tested?
ibritumomab tiuxetan, rituximab and melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
10 sitesSwitzerland
Study dates
Oct 2006to May 2013
Phase
Phase 1
Are there results?
None posted in the registry

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 65 to 120 years
  • All sexes
  • No healthy volunteers
  • Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed non-Hodgkin's lymphoma of any type
  • CD20-positive disease
  • Achieved partial or complete response to salvage treatment for relapse or refractory disease within the past 10 weeks
  • Must have an indication for autologous stem cell transplantation
  • Bone marrow infiltration < 25%
  • No evidence of CNS involvement

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • AST ≤ 2 times ULN
  • Creatinine clearance > 50 mL/min
  • No clinically significant cardiac disease, including any of the following:
  • Unstable angina pectoris
  • Significant arrhythmia
  • Myocardial infarction within the past 3 months
  • LVEF > 50%
  • No clinically significant urinary tract obstruction
  • No clinically significant pulmonary disease
  • No serious underlying medical condition that would preclude study participation
  • No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated in situ cervical cancer

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 30 days since prior participation in another clinical trial
  • No prior stem cell transplantation
  • No prior radiolabeled antibodies, including for induction of disease remission
  • No prior radiotherapy to ≥ 25% of the bone marrow
  • No concurrent radiotherapy
  • No other concurrent anticancer drugs
  • No other concurrent investigational drugs

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Switzerland10 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Saint Claraspital AG

    Basel, 4016

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

    Bellinzona, 6500

  • Inselspital Bern

    Bern, 3010

  • Kantonsspital Liestal

    Bern, CH-3008

  • Kantonsspital Bruderholz

    Bruderholz, 4101

  • Hopital Cantonal Universitaire de Geneve

    Geneva, CH-1211

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

Other trials in Switzerland

About this study

Official title: Ibritumomab Tiuxetan and High-Dose Melphalan as Conditioning Regimen Before Autologous Stem Cell Transplantation for Elderly Patients With Lymphoma in Relapse or Resistant to Chemotherapy. A Multicenter Phase I Trial

RATIONALE: Giving chemotherapy drugs, such as melphalan, before an autologous stem cell transplant helps stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Also, monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Chemotherapy and monoclonal antibody therapy also prepares the patient's bone marrow for the stem cell transplant. Giving colony-stimulating factors, such as G-CSF, and vinorelbine helps stem cells move from the bone marrow to the blood so they can be collected and stored. The stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and monoclonal antibody therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab followed by autologous stem cell transplant in treating older patients with non-Hodgkin's lymphoma that has relapsed or not responded to previous treatment.

Read the detailed description

OBJECTIVES:

  • Determine the maximum tolerated dose of high-dose melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab as a conditioning regimen followed by vinorelbine ditartrate- and filgrastim (G-CSF)-mobilized autologous stem cell transplantation in elderly patients with relapsed or refractory CD20-positive non-Hodgkin's lymphoma.
  • Evaluate the feasibility and safety of this regimen in these patients.
  • Determine the feasibility of stem cell mobilization with vinorelbine ditartrate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of high-dose melphalan.

  • Stem cell harvest and mobilization: Patients receive vinorelbine ditartrate IV on day -36 and filgrastim (G-CSF) subcutaneously (SC) twice daily on days -33 to -29. Patients undergo peripheral blood stem cell harvest on days -29 to -26.
  • Radioimmunotherapy: Patients receive rituximab IV. Within 4 hours after completion of rituximab, patients receive indium In 111 ibritumomab tiuxetan (imaging dose) IV over 10 minutes on day -25. Patients undergo assessment of biodistribution, imaging, and dosimetry on days -25, -22, and optionally on day -20. Patients with acceptable biodistribution of indium In 111 ibritumomab tiuxetan receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (therapeutic dose) IV over 10 minutes on day -18.
  • High-dose chemotherapy: Patients receive high-dose melphalan IV on day -1. Cohorts of 3-6 patients receive escalating doses of high-dose melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
  • Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed for 100 days.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Conditions
Lymphoma
Being tested
ibritumomab tiuxetan, rituximab, melphalan, vinorelbine tartrate / G-CSF, autologous hematopoietic stem cell harvesting and transplantation
Keywords
recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, Waldenström macroglobulinemia
Medical subject headings
Lymphoma, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

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

  • ibritumomab tiuxetanDrug

    Also called ZEVALIN

    185 MBq (5mCi) of 111In-Zevalin will be used for radioimaging. and the dose is 14.8 MBq/kg (0.4 mCi/kg) total body weight of 90Y-Zevalin (max. 1184 MBq or 32 mCi at patients > 80kg) for imaging.

  • rituximabDrug

    Also called MabThera

    250 mg/m2

  • melphalanDrug

    Also called Alkeran

    • Dose level 1: 100 mg/m2
    • Dose level 2: 140 mg/m2
    • Dose level 3: 170 mg/m2
    • Dose level 4: 200 mg/m2

  • vinorelbine tartrate / G-CSFDrug

    Also called Navelbine

    on day 1: 35 mg/m2 day 4-8 (longer if required) G-CSF 5 μg/kg s.c. morning and 5 μg/kg s.c. evening for at least 5 days

  • autologous hematopoietic stem cell harvesting and transplantationProcedure or surgery

    Optimal mobilization usually takes place on day 8. A minimum of 2.5x106 CD34+ cells/kg should be collected (optimal 5x106 CD34+ cells/kg). If not enough CD34+ cells can be collected on day 8, it is recommended to continue with G-CSF until a sufficient collection (a minimum of 2.5x106 CD34+ cells/kg) can be obtained.

    Stem cells will be reinfused approximately 24 hours after the melphalan administration. The infusion will be performed with a minimum of 2.5x106 CD34+ cells/kg body weight according to local guidelines. G-CSF (5 μg/kg/d) will be given from day 5 and continued until neutrophils > 0.5x109/l for at least 2 consecutive days.

Study groups in NCT00392691
Study groupRoleWhat they receive
Zevalin, Rituximab, MelphalanExperimentalNot described
Receives: Drug: ibritumomab tiuxetan; Drug: rituximab; Drug: melphalan; Drug: vinorelbine tartrate / G-CSF; Procedure: autologous hematopoietic stem cell harvesting and transplantation

What is being measured

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

  1. Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan

    Measured: within 8 weeks after application of melphalan

Secondary outcomes (3)

  1. Toxicity

    Measured: 100 days (+/- 5 days) after reinfusion of stem cells

  2. Event occurrence up to 100 days after transplantation

    Measured: up to 100 days after transplantation

  3. Complete remission 100 days after transplantation

    Measured: 100 days after transplantation

Timeline

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

  1. First posted26 Oct 2006 (estimated)
  2. Study startOct 2006
  3. Primary completionDec 2012
  4. Study completionMay 2013

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00392691
Sponsor's protocol ID
SAKK 37/05
Other IDs
SWS-SAKK-37/05, EU-20648, SPRI-SWS-SAKK-37/05, CDR0000511915
Status last verified
May 2019
First submitted
25 Oct 2006
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No

Publications

  • Voegeli M, Rondeau S, Berardi Vilei S, Lerch E, Wannesson L, Pabst T, Rentschler J, Bargetzi M, Jost L, Ketterer N, Bischof Delaloye A, Ghielmini M. Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05). Hematol Oncol. 2017 Dec;35(4):576-583. doi: 10.1002/hon.2348. Epub 2016 Sep 28.

    PubMed 27677906

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ibritumomab tiuxetan, rituximab and melphalan in people with Lymphoma, run by Swiss Cancer Institute at 10 sites in Switzerland.

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

Who may be eligible to take part?

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 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Switzerland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan (time frame: within 8 weeks after application of melphalan). 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 NCT00392691, 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 15 May 2019.

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