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

NCT00392691 | Completed Phase 1

• 5 other identifiers: SAKK 37/05SWS-SAKK-37/05EU-20648SPRI-SWS-SAKK-37/05CDR0000511915
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

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.

Conditions

Lymphoma

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

Outcome Measures

Primary Outcomes (1)

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

  within 8 weeks after application of melphalan

Secondary Outcomes (3)

• Toxicity

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

• Event occurrence up to 100 days after transplantation

  up to 100 days after transplantation

• Complete remission 100 days after transplantation

  100 days after transplantation

Study Arms (1)

Zevalin, Rituximab, Melphalan

EXPERIMENTAL

Drug: ibritumomab tiuxetan; Drug: rituximab; Drug: melphalan; Drug: vinorelbine tartrate / G-CSF; Procedure: autologous hematopoietic stem cell harvesting and transplantation

Interventions

ibritumomab tiuxetan 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.

Also known as: ZEVALIN

Zevalin, Rituximab, Melphalan

rituximab DRUG

250 mg/m2

Also known as: MabThera

Zevalin, Rituximab, Melphalan

melphalan 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

Also known as: Alkeran

Zevalin, Rituximab, Melphalan

vinorelbine tartrate / G-CSF 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

Also known as: Navelbine

Zevalin, Rituximab, Melphalan

autologous hematopoietic stem cell harvesting and transplantation 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.

Zevalin, Rituximab, Melphalan

Eligibility Criteria

• Age: 65 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (10)

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Saint Claraspital AG

Basel, 4016, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Liestal

Bern, CH-3008, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, 4101, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Related 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. 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.

  PMID: 27677906 RESULT

MeSH Terms

Conditions

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; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

ibritumomab tiuxetan; Rituximab; Melphalan; Vinorelbine; Granulocyte Colony-Stimulating Factor; Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Surgical Procedures, Operative

Study Officials

• Michele Voegeli, MD

  Kantonsspital Liestal

  STUDY CHAIR

• Michele Ghielmini, Prof

  IOSI, Ospedale San Giovanni

  STUDY CHAIR

• Angelika Bischof Delaloye, Prof

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2013
• Last Updated: May 15, 2019

Record last verified: 2019-05

Locations

CH (10)