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

NCT ID: NCT00392691

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2013-05-31

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Zevalin, Rituximab, Melphalan

Group Type: EXPERIMENTAL

ibritumomab tiuxetan

Intervention Type: DRUG

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

Intervention Type: DRUG

250 mg/m2

melphalan

Intervention Type: DRUG

• 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

Intervention Type: DRUG

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 transplantation

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DRUG

rituximab

250 mg/m2

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

ZEVALIN; MabThera; Alkeran; Navelbine

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Voegeli, MD

Role: STUDY_CHAIR

Kantonsspital Liestal

Michele Ghielmini, Prof

Role: STUDY_CHAIR

IOSI, Ospedale San Giovanni

Angelika Bischof Delaloye, Prof

Role: STUDY_CHAIR

Faculté de biologie et de médecine de l' Université de Lausanne

Locations

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

Sankt Gallen, , Switzerland

Countries

Switzerland

References

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.

Reference Type: RESULT

PMID: 27677906 (View on PubMed)

Other Identifiers

SWS-SAKK-37/05

Identifier Type: -

Identifier Source: secondary_id

EU-20648

Identifier Type: -

Identifier Source: secondary_id

SPRI-SWS-SAKK-37/05

Identifier Type: -

Identifier Source: secondary_id

CDR0000511915

Identifier Type: -

Identifier Source: secondary_id

SAKK 37/05

Identifier Type: -

Identifier Source: org_study_id