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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00392691
• Other study ID #: SAKK 37/05
• Secondary ID: SWS-SAKK-37/05EU
• Status: Completed
• Phase: Phase 1
• Start date: October 2006
• Est. completion date: May 2013

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• ibritumomab tiuxetan
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.
• rituximab
250 mg/m2
• melphalan
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-CSF
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

Procedure:
• autologous hematopoietic stem cell harvesting and transplantation
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.

Locations

Country	Name	City	State
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Saint Claraspital AG	Basel
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Liestal	Bern
Switzerland	Kantonsspital Bruderholz	Bruderholz
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital - St. Gallen	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

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. Y(90) -Ibritumomab tiuxetan (Y(90) -IT) and high-dose melphalan as conditioning regimen before autologous — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan		within 8 weeks after application of melphalan
Secondary	Toxicity		100 days (+/- 5 days) after reinfusion of stem cells
Secondary	Event occurrence up to 100 days after transplantation		up to 100 days after transplantation
Secondary	Complete remission 100 days after transplantation		100 days after transplantation