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

Phase

Condition

Multiple Myeloma

Cancer/tumors

Hematologic Cancer

Treatment

N/A

Clinical Study ID

NCT00637767

CDR0000588063

EU-20820

2006-003424-12

Ages 18-120
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

DISEASE CHARACTERISTICS:

Histologically or cytologically proven multiple myeloma (MM)
Scheduled to undergo autologous hematopoietic stem cell transplantation (HSCT) as consolidation treatment for MM
Must have sufficient CD34-positive stem cells (≥ 4 x 10^6 cells per kg body weight) in cryo-storage for two autologous HSCTs
In partial remission (PR) after prior chemotherapy but before priming therapy for stem cell mobilization
Patients in complete remission (CR) after prior chemotherapy are not eligible
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

Study Design

December 01, 2007

October 31, 2013

Study Description

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
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.

Connect with a study center

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England B15 2TH
United Kingdom
Site Not Available
Saint Bartholomew's Hospital
London, England EC1A 7BE
United Kingdom
Site Not Available
Southampton General Hospital
Southampton, England SO16 6YD
United Kingdom
Site Not Available

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