Myeloma X Relapse (Intensive): A Phase III Study to Determine the Role of a Second Autologous Stem Cell Transplant as Consolidation Therapy in Patients With Relapsed Multiple Myeloma Following Prior High-dose Chemotherapy and Autologous Stem Cell Rescue.
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
Myeloma X Relapse (Intensive): A Phase III Study to Determine the Role of a Second Autologous Stem Cell Transplant as Consolidation Therapy in Patients With Relapsed Multiple Myeloma Following Prior High-dose Chemotherapy and Autologous Stem Cell Rescue.
OBJECTIVES:
Primary
- To determine the effect on freedom from disease progression in patients with relapsed
multiple myeloma treated with re-induction therapy comprising bortezomib, doxorubicin
hydrochloride, and dexamethasone (PAD) followed by a second autologous stem cell
transplantation (ASCT) with high-dose melphalan vs low-dose cyclophosphamide
consolidation therapy.
Secondary
- To assess the response rate of PAD in patients following a previous autograft.
- To compare the overall response rate of patients following high-dose melphalan
chemotherapy and autologous stem cell transplantation with low-dose cyclophosphamide
consolidation therapy.
- To assess the overall survival of patients treated with this regimen.
- To assess the safety and toxicity of a second ASCT in these patients.
- To assess the safety and toxicity of PAD in these patients.
- To assess the feasibility of stem cell collection following PAD in these patients.
- To determine the impact of this regimen on pain and quality of life in these patients.
OUTLINE: This is a multicenter study.
- Re-induction (PAD) therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11,
doxorubicin hydrochloride IV continuously on days 1-4, and oral dexamethasone on days
1-4 (and days 8-11 and 15-18 of course 1 only). Treatment repeats every 21 days for up
to 4 courses in the absence of disease progression or unacceptable toxicity.
- Peripheral blood stem cell (PBSC) mobilization and harvest: Within 6-12 weeks, some
patients receive cyclophosphamide IV on day 0 and filgrastim (G-CSF) subcutaneously
(SC) beginning on day 1 and continuing to time of PBSC harvest. PBSCs are then
collected.
Patients who successfully complete re-induction therapy and have adequate PBSC mobilization
are stratified according to length of first remission or plateau (≤ vs ≥ 24 months) and
response to PAD re-induction therapy (stable disease vs ≥ partial response). Patients are
randomized to 1 of 2 arms.
- Arm I (high-dose melphalan consolidation therapy): Patients receive high-dose melphalan
IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.
- Arm II (low-dose cyclophosphamide consolidation therapy): Patients receive low-dose
cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.
Patients complete the EORTC QLQ-C30 and EORTC QLQ-MY20, the Brief Pain Inventory Short Form
(BPI-SF), and the Leeds Assessment of Neuropathic Symptoms and Signs (Self Assessment) Pain
Scale (S-LANSS) questionnaires at baseline and after completion of re-induction therapy.
Patients are followed monthly for up to 100 days after ASCT or at 30 days after low-dose
cyclophosphamide and then every 3 months for 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of relapsed multiple myeloma
- Symptomatic disease, including non-secretory
- Previously treated with standard chemotherapy and autologous stem cell
transplantation
- Requires therapy for first progressive disease AND at least 18 months since first
stem cell transplantation
- Patients who were previously immunofixation-negative and are now
immunofixation-positive must have > 5 g/L absolute increase in paraprotein
- Registered in the Myeloma X Relapse (Intensive) Trial and received 2-4 courses of PAD
re-induction chemotherapy according to the protocol (consolidation phase)
- Adequate stem cell mobilization available for transplantation defined as ≥ 2x10^6
CD34 + cells/kg or ≥ 2x10^8 PBMC/kg including cells stored from a previous harvest
(consolidation phase)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1 x 10^9/L
- Platelet count ≥ 50 x 10^9/L
- Creatinine clearance ≥ 30 mL/min
- Total bilirubin < 2 times upper limit of normal (ULN)
- ALT or AST < 2.5 times ULN
- History of pulmonary disease allowed provided carbon monoxide diffusion in the lungs
(KCO/DLCO) is ≥ 50% and/or no requirement for supplementary continuous oxygen
- Left ventricular ejection fraction ≥ 40% by ECG or MUGA scan
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment
- No peripheral neuropathy ≥ grade 2
- No known HIV or Hepatitis B or C positivity (testing is not required)
- No known resistance to combined bortezomib, doxorubicin hydrochloride, and
dexamethasone therapy
- No known history of allergy to compounds containing boron or mannitol
- No other previous or concurrent malignancies except for appropriately treated
localized epithelial skin cancer or carcinoma in situ of the cervix, or remote
histories of other cured tumors within the past 5 years
- No medical or psychiatric condition which, in the opinion of the investigator,
contraindicates the patient's participation in the study
- No other contra-indication to treatment that would make the patient ineligible for
consolidation phase
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No other prior therapy for relapsed disease except for local radiotherapy,
therapeutic plasma exchange, or ≤ 200 mg of dexamethasone
- Radiotherapy since prior transplantation sufficient to alleviate or control pain
of local invasion is permitted
- No hemi-body radiation since prior transplantation (consolidation phase)
- At least 4 weeks since prior and no concurrent investigational drugs
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to disease progression
Safety Issue:
No
Principal Investigator
Gordon Cook, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Leeds Cancer Centre at St. James's University Hospital
Authority:
Unspecified
Study ID:
CDR0000612567
NCT ID:
NCT00747877
Start Date:
April 2008
Completion Date:
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- stage I multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
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