High-Dose Melphalan and a Second Stem Cell Transplant or Low-Dose Cyclophosphamide in Treating Patients With Relapsed Multiple Myeloma After Chemotherapy - Full Text View

Sponsored by:	Leeds Cancer Centre at St. James's University Hospital
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00747877

Purpose

RATIONALE: Giving chemotherapy and bortezomib before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and bortezomib. It is not yet known whether high-dose melphalan given together with a second stem cell transplant is more effective than low-dose cyclophosphamide in treating patients with relapsed multiple myeloma.

PURPOSE: This randomized phase III trial is studying giving high-dose melphalan together with a second stem cell transplant to see how well it works compared with low-dose cyclophosphamide in treating patients with relapsed multiple myeloma after chemotherapy.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: cyclophosphamide Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation	Phase III

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Cyclophosphamide Melphalan Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	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.

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

Primary Outcome Measures:

Time to disease progression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate to bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) [ Designated as safety issue: No ]
Overall response rate following randomized treatments [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Toxicity and safety of autologous stem cell transplantation [ Designated as safety issue: Yes ]
Toxicity and safety of weekly cyclophosphamide [ Designated as safety issue: Yes ]
Toxicity and safety of PAD therapy [ Designated as safety issue: Yes ]
Feasibility of stem cell collection [ Designated as safety issue: No ]
Pain [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	460
Study Start Date:	April 2008
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.	Drug: melphalan Given IV Procedure: autologous hematopoietic stem cell transplantation Patients undergo autologous hematopoietic stem cell transplantation on day 0.
Arm II: Experimental Patients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.	Drug: cyclophosphamide Given orally

Detailed Description:

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747877

Locations

United Kingdom, England
Leeds Cancer Centre at St. James's University Hospital	Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Gordon Cook, MD, PhD 44-113-206-7940
Nottingham City Hospital NHS Trust	Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: Cathy Williams, MD 44-115-969-1169 ext. 34666
Royal Hallamshire Hospital	Recruiting
Sheffield, England, United Kingdom, S1O 2JF
Contact: John Snowden, MD 44-114-271-3357
Saint Bartholomew's Hospital	Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Jamie Cavenagh, MD 44-207-601-8202
United Kingdom, Northern Ireland
Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Recruiting
Belfast, Northern Ireland, United Kingdom, BT9 7AB
Contact: Curly Morris 44-28-9026-3733
United Kingdom, Scotland
Pinderfields General Hospital	Recruiting
Wakefield, Scotland, United Kingdom, WF1 4DG
Contact: John Ashcroft, MD 44-1924-212-443

Sponsors and Collaborators

Leeds Cancer Centre at St. James's University Hospital

Investigators

Principal Investigator:

Gordon Cook, MD, PhD

Leeds Cancer Centre at St. James's University Hospital

More Information

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

Study ID Numbers:	CDR0000612567, LCC-HM05/7287, EU-20873, ISRCTN60123120, EudraCT-2006-005890-24
Study First Received:	September 4, 2008
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00747877
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Melphalan
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias

Cyclophosphamide
Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Therapeutic Uses
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009