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

Sponsor:	Southampton University Hospitals NHS Trust
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00637767

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation Radiation: yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomised Phase II Clinical Trial Using Targeted Radiotherapy Delivered by an Yttrium-90 Radio-Labelled Anti-CD66 Monoclonal Antibody With High Dose Melphalan Compared to Melphalan Alone, Prior to Autologous Stem Cell Transplantation for Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Immunoglobulins Melphalan Sarcolysin Melphalan hydrochloride Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Remission status pre- and post-transplantation, specifically the number of patients who achieve complete remission, as measured by the European Blood and Marrow Transplantation Organization Response Criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease response, as measured by changes in serum free light chains (in those patients with serum free light chains that are informative) [ Designated as safety issue: No ]
Disease response, including the proportion of patients with partial remission, stable disease, and progressive disease and remission duration (time to disease progression) [ Designated as safety issue: No ]
Engraftment quality, as measured by time to recovery of peripheral blood neutrophils to > 500/mm³ and platelets > 50, 000/mm³ and duration of recovery for > 180 days post-transplantation [ Designated as safety issue: No ]
Treatment-related mortality [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous stem cell transplantation [ Designated as safety issue: Yes ]
Pharmacokinetics of indium In 111 anti-CD66 monoclonal antibody BW250/183 as measured by serial blood samples and serial planar and single-photon emission computed tomography (SPECT) gamma camera imaging of selected organs [ Designated as safety issue: No ]
Development of a dosimetry model based on SPECT and whole body gamma camera imaging [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	December 2007
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed 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 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637767

Locations

United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Recruiting
Birmingham, England, United Kingdom, B15 2TH
Contact: Contact Person 44-121-472-1311
Saint Bartholomew's Hospital	Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Contact Person 44-20-7377-7000
Southampton General Hospital	Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Kim Orchard, MD 44-0-238-079-4118 kho@soton.ac.uk

Sponsors and Collaborators

Southampton University Hospitals NHS Trust

Investigators

Study Chair:

Kim Orchard, MD

Southampton University Hospitals NHS Trust

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00637767 History of Changes
Other Study ID Numbers:	CDR0000588063, USCTU-ANTI-CD66, Eudract-2006-003424-12, EU-20820
Study First Received:	March 14, 2008
Last Updated:	July 7, 2009
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Antibodies
Immunoglobulins
Antibodies, Monoclonal
Melphalan
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Myeloablative Agonists
Immunosuppressive Agents
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012