Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active Over 18 Other USCTU-ANTI-CD66 USCTU-ANTI-CD66, Eudract-2006-003424-12, EU-20820, NCT00637767

Objectives

Primary

1. 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

1. To determine the toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous hematopoietic stem cell transplantation.
2. 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.
3. 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.
4. To investigate the pharmacokinetic behavior of indium In 111 anti-CD66 monoclonal antibody BW250/183 (used for dosimetry).
5. 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).
6. 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.

Entry 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 10⁶ 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%

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

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

Expected Enrollment

Outcomes

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

Disease response, as measured by changes in serum free light chains (in those patients with serum free light chains that are informative)
Disease response, including the proportion of patients with partial remission, stable disease, and progressive disease and remission duration (time to disease progression)
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
Treatment-related mortality
Overall survival
Toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody BW250/183 in the context of autologous stem cell transplantation
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
Development of a dosimetry model based on SPECT and whole body gamma camera imaging
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.

Trial Contact Information

Trial Lead Organizations

Southampton General Hospital

Kim Orchard, MD, Protocol chair		Ph: 44-0-238-079-4118 Email: kho@soton.ac.uk

United Kingdom
England
	Birmingham
	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
		Contact Person	Ph:  44-121-472-1311
	London
	Saint Bartholomew's Hospital
		Contact Person	Ph:  44-20-7377-7000
	Southampton
	Southampton General Hospital
		Kim Orchard, MD	Ph:  44-0-238-079-4118
			Email: kho@soton.ac.uk

Registry Information
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
Trial Start Date		2007-12-12
Trial Completion Date		2010-12-17 (estimated)
Registered in ClinicalTrials.gov		NCT00637767
Date Submitted to PDQ		2008-02-19
Information Last Verified		2008-03-30