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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

Kim Orchard, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospital Southampton NHS Foundation Trust.

Authority:

Unspecified

Study ID:

CDR0000588063

NCT ID:

NCT00637767

Start Date:

December 2007

Completion Date:

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

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