High-Dose Chemotherapy and Stem Cell Transplant in Treating Patients With Newly Diagnosed Stage I, Stage II, or Stage III Multiple Myeloma

Sponsor

Erasme University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00526734

Collaborator

(none)

100

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan, use different ways to stop cancer cells from dividing so they stop growing or die. Stem cell transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Giving colony-stimulating factors, such as G-CSF or pegfilgrastim, helps stem cells move from the bone marrow to the blood so they can be collected. It is not yet known which regimen is more effective in treating multiple myeloma.

PURPOSE: This randomized phase II trial is studying how well high-dose chemotherapy followed by stem cell transplant works in treating patients with newly diagnosed stage I, stage II, or stage III multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Biological: pegfilgrastim Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

Compare engraftment of peripheral blood progenitor cells (PBPCs) mobilized by 2 different fixed doses of pegfilgrastim versus a by-weight dose of filgrastim (G-CSF).

Secondary

Determine the ability of 2 different fixed doses of pegfilgrastim to mobilize PBPCs.
Determine the safety of pegfilgrastim during PBPC mobilization and collection.
Determine the effect of different induction chemotherapy regimens on autologous progenitor cell transplantation.

OUTLINE: This is a multicenter study. Patients are stratified by type of induction chemotherapy (Thal/Dex vs VAD vs Vel-Dex vs VTD) and by stage of disease according to International Prognostic Index criteria (stage I [i.e., beta-2 microglobulin < 3.5 and albumin > 35] vs stages II and III).

Induction therapy: Patients receive 3-4 courses of 1 of the following regimens:
VAD: Patients receive vincristine, doxorubicin hydrochloride, and dexamethasone.
Thal/Dex: Patients receive thalidomide and dexamethasone.
Vel-Dex: Patients receive bortezomib and dexamethasone.
VTD: Patients receive bortezomib, thalidomide, and dexamethasone. Patients achieving complete, partial, or minimal response after 3-4 courses of induction therapy proceed to peripheral blood progenitor cell (PBPC) mobilization 17 days after completion of induction therapy.
PBPC mobilization: Patients are randomized to 1 of 3 arms.
Arm I: Patients receive filgrastim subcutaneously (SC) once daily until the final leukapheresis.
Arm II: Patients receive a single dose of pegfilgrastim SC.
Arm III: Patients receive pegfilgrastim as in arm II at a higher dose.
Leukapheresis: Patients undergo up to 3 leukaphereses to obtain adequate numbers of CD34-positive filgrastim- or pegfilgrastim-mobilized PBPCs for engraftment. Patients achieving a sufficient number of collected PBSCs proceed to conditioning chemotherapy.
Conditioning chemotherapy: Patients receive high-dose melphalan* IV over 1-2 days. Patients then proceed to PBPC transplantation.

NOTE: *Patients ≥ 65 years old receive melphalan at a lower dose.

Autologous PBPC transplantation: Patients undergo infusion of PBPCs on day 0. Patients in all arms receive G-CSF support beginning on day 1 after PBPC transplantation and continuing until blood counts recover for 3 consecutive days.

After completion of study therapy, patients are followed for up to 100 days post-transplantation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised, International, Open-label, Phase II Study of Peripheral Blood Progenitor Cell (PBPC) Mobilization and Engraftment With Pegfilgrastim or Filgrastim for Autologous Transplantation in Patients With Multiple Myeloma (MM)

Study Start Date :

Feb 1, 2006

Outcome Measures

Primary Outcome Measures

Number of patients with engraftment after induction chemotherapy []

Secondary Outcome Measures

Number and proportion of patients from whom ≥ 2 x 10e6 CD34-positive cells/kg are harvested []
Number and proportion of patients from whom ≥ 4 x 10e6 CD34-positive cells/kg are harvested []
CD34-positive cells/kg yield in each leukapheresis []
Number of leukaphereses to collect ≥ 2 x 10e6 CD34-positive cells/kg []
Number of leukaphereses to collect ≥ 4 x 10e6 CD34-positive cells/kg []
Proportion of patients with platelet recovery ≥ 20 x 10e9/L in the absence of transfusion for at least 7 days []
Proportion of patients with ANC recovery of ≥ 0.5 x 10e9/L []
Time to neutrophil recovery, defined as the time to neutrophil engraftment (i.e., ANC ≥ 0.5 x 10e9/L for 3 consecutive days) []
Time to ANC ≥ 1.0 x 10e9/L []
Time to platelet recovery, defined as the time to platelets ≥ 20 x 10e9/L in the absence of platelet transfusion support for at least 7 days []
Incidence and duration of hospitalization during mobilization phase and during post-transplantation phase []
Incidence and severity of adverse events during and after the use of pegfilgrastim 12 mg or pegfilgrastim 18 mg and filgrastim []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of symptomatic stage I or stage II-III multiple myeloma
Newly diagnosed disease
No amyloidosis

PATIENT CHARACTERISTICS:

Inclusion criteria:

ECOG performance status 0-2
ANC ≥ 1.0 x 10^9/L (without colony-stimulating factors)
Platelet count ≥ 50 x 10^9/L (without transfusion support within the past 7 days)
Serum calcium < 14 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 times ULN
Creatinine clearance ≥ 50 mL/min
Fertile patients must use effective contraception
Negative pregnancy test
Willing and able to comply with protocol requirements

Exclusion criteria:

Myocardial infarction within the past 6 months
New York Heart Association class III or IV heart failure
Uncontrolled angina
Severe uncontrolled ventricular arrhythmia
Acute ischemia or active conduction system abnormalities as evidenced by ECG
Serious medical condition that could prolong hematological recovery or preclude completion of or tolerance to protocol therapy
Seropositive for HIV antibody
Known hepatitis B surface antigen positivity OR active hepatitis C infection
Active systemic infection requiring treatment
Pregnant or nursing
Poor psychiatric condition

PRIOR CONCURRENT THERAPY:

No plasmapheresis within the past 4 weeks
No major surgery within the past 4 weeks
No anticancer therapy within the past 5 years, except treatment for basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix
No other concurrent G-CSF growth factors
No concurrent enrollment in another investigational clinical trial
No concurrent investigational agent that would contraindicate the use of pegfilgrastim as either a mobilization agent or a hematological recovery agent

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Universitaire Erasme	Brussels	Belgium	1070
2	Medical University of Gdansk	Gdansk	Poland	80-211
3	Silesian Medical Academy	Katowice	Poland	40-029
4	Institute of Haematology and Blood Transfusion	Warsaw	Poland	00-957