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

Phase 2
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Registration Number
NCT00526734
Lead Sponsor
Erasme University Hospital
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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Number of patients with engraftment after induction chemotherapy
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (4)

Medical University of Gdansk

🇵🇱

Gdansk, Poland

Institute of Haematology and Blood Transfusion

🇵🇱

Warsaw, Poland

Hopital Universitaire Erasme

🇧🇪

Brussels, Belgium

Silesian Medical Academy

🇵🇱

Katowice, Poland

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