High-Dose Melphalan With or Without Radiolabeled Monoclonal Antibody in Treating Patients With Multiple Myeloma Undergoing an Autologous Stem Cell Transplant

NCT ID: NCT00637767

Last Updated: 2020-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-01

Study Completion Date

2013-10-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. A stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by the chemotherapy and radiolabeled monoclonal antibody.

PURPOSE: This randomized phase II trial is studying how well high-dose melphalan works when given with or without radiolabeled monoclonal antibody in treating patients with multiple myeloma undergoing an autologous stem cell transplant.

Detailed Description

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OBJECTIVES:

Primary

* To determine the efficacy of high-dose melphalan (200mg/m²) in combination with targeted radiotherapy delivered by yttrium Y 90 anti-CD66 monoclonal antibody BW250/183, in terms of disease response (complete remission rate and change in serum free light chain level before and after treatment with yttrium Y 90 anti-CD66 monoclonal antibody BW250/183), in patients undergoing autologous hematopoietic stem cell transplantation for multiple myeloma.

Secondary

* To determine the toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous hematopoietic stem cell transplantation.
* To determine the effect of targeted radiotherapy on other parameters of disease response, in terms of proportion of patients with partial remission, stable disease, and progressive disease, remission duration (time to disease progression), and overall survival.
* To determine the effect of targeted radiotherapy on engraftment when used in combination with high-dose melphalan in patients undergoing autologous hematopoietic stem cell transplantation for multiple myeloma.
* To investigate the pharmacokinetic behavior of indium In 111 anti-CD66 monoclonal antibody BW250/183 (used for dosimetry).
* To continue to develop a dosimetry model based on single-photon emission computed tomography (SPECT) and whole body gamma camera imaging following administration of the radiolabeled anti-CD66 monoclonal antibody (in a subset of patients at the Southampton site only).
* To assess the proportion of patients who form human anti-murine antibodies (HAMA) after treatment with targeted radiotherapy in the context of an autologous hematopoietic stem cell transplantation.

OUTLINE: This is a multicenter study. Patients are stratified according to disease risk group (low risk \[beta-2 microglobulin and C-reactive protein \< 6 or either beta-2 microglobulin or C-reactive protein ≥ 6\] vs high risk \[both beta-2 microglobulin and C-reactive protein ≥ 6\]). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive a dosimetry dose of indium In 111 anti-CD66 monoclonal antibody BW250/183 IV on day 1 and undergo gamma camera imaging and serial blood samples on days 1-5. Patients then receive a therapeutic dose of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 IV once between days 9 and 16 and high-dose melphalan IV on day 28. Patients then undergo autologous hematopoietic stem cell transplantation (HSCT) on day 30.
* Arm II: Patients receive high-dose melphalan IV on day 1. Patients then undergo autologous HSCT on day 3.

Patients in arm I undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies and analysis of human anti-murine antibody (HAMA) status.

After completion of study treatment, patients are followed periodically.

Conditions

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Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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radio-labelled anti-CD66 monoclonal antibody

Up to 4mg radio-labelled anti-CD66 monoclonal antibody. Plus standard treatment

Group Type EXPERIMENTAL

melphalan

Intervention Type DRUG

autologous hematopoietic stem cell transplantation

Intervention Type PROCEDURE

yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183

Intervention Type RADIATION

No IMP - standard treatment

No IMP - standard treatment

Group Type ACTIVE_COMPARATOR

melphalan

Intervention Type DRUG

autologous hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Interventions

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melphalan

Intervention Type DRUG

autologous hematopoietic stem cell transplantation

Intervention Type PROCEDURE

yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Bone marrow cellularity ≥ 20%

PATIENT CHARACTERISTICS:

* WHO performance status 0-1
* Life expectancy ≥ 24 weeks
* Hemoglobin ≥ 9.0 g/dL
* Neutrophils ≥ 1,500/mm³
* Platelets ≥ 50,000/mm³
* Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT and/or AST ≤ 2.5 times ULN
* Creatinine clearance ≥ 50 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile female patients must use effective contraception for 4 weeks prior to, during, and for 6 months after completion of study treatment
* Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
* Able to cooperate with study treatment and follow up
* Human anti-mouse antibody (HAMA) negative
* No active uncontrolled infection
* No high-risk non-malignant systemic disease
* No other condition, that in the investigator's opinion, would make the patient an unsuitable candidate for the study
* No known HIV or hepatitis B or C seropositivity
* No history of allergy, including an allergy to rodents or rodent proteins
* No history of eczema or asthma
* No history of New York Heart Association (NYHA) class III or IV cardiac disease
* No congestive heart failure

PRIOR CONCURRENT THERAPY:

* Recovered from prior therapy

* Alopecia or certain grade 1 toxicities allowed
* More than 4 weeks since prior radiotherapy (except for localized pain control), endocrine therapy, or immunotherapy
* More than 4 weeks since prior and no other concurrent chemotherapy for the underlying hematological condition, except for the following:

* Cyclophosphamide as priming for stem cell harvest
* Thalidomide
* More than 3 weeks since prior major thoracic and/or abdominal surgery and recovered
* No prior high-dose therapy and autologous HSCT
* Concurrent radiotherapy allowed for the control of bone pain

* The irradiated lesions are not used for response evaluation
* No other concurrent anti-cancer therapy or investigational drugs during transplantation conditioning
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NIHR Clinical Research Facility, University Hospital Southampton NHS Foundation Trust

UNKNOWN

Sponsor Role collaborator

European Federation of Pharmaceutical Industries and Associations

UNKNOWN

Sponsor Role collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

The Periscope Consortium

UNKNOWN

Sponsor Role collaborator

Q-Biologicals NV

UNKNOWN

Sponsor Role collaborator

University of Southampton

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kim Orchard, MD

Role: STUDY_CHAIR

University Hospital Southampton NHS Foundation Trust

Locations

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Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, United Kingdom

Site Status

Saint Bartholomew's Hospital

London, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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2006-003424-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EU-20820

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000588063

Identifier Type: -

Identifier Source: org_study_id