Clinical trial NCT00526734: High-Dose Chemotherapy and Stem Cell Transplant in Treating Patients With Newly Diagnosed Stage I, Stage II, or Stage III Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-09-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with engraftment after induction chemotherapy
Secondary outcomes:
measure: Number and proportion of patients from whom ≥ 2 x 10e6 CD34-positive cells/kg are harvested
measure: Number and proportion of patients from whom ≥ 4 x 10e6 CD34-positive cells/kg are harvested
measure: CD34-positive cells/kg yield in each leukapheresis
measure: Number of leukaphereses to collect ≥ 2 x 10e6 CD34-positive cells/kg
measure: Number of leukaphereses to collect ≥ 4 x 10e6 CD34-positive cells/kg
measure: Proportion of patients with platelet recovery ≥ 20 x 10e9/L in the absence of transfusion for at least 7 days
measure: Proportion of patients with ANC recovery of ≥ 0.5 x 10e9/L
measure: Time to neutrophil recovery, defined as the time to neutrophil engraftment (i.e., ANC ≥ 0.5 x 10e9/L for 3 consecutive days)
measure: Time to ANC ≥ 1.0 x 10e9/L
measure: 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
measure: Incidence and duration of hospitalization during mobilization phase and during post-transplantation phase
measure: Incidence and severity of adverse events during and after the use of pegfilgrastim 12 mg or pegfilgrastim 18 mg and filgrastim
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Katowice
country: Poland
facility: Silesian Medical Academy
city: Warsaw
country: Poland
facility: Institute of Haematology and Blood Transfusion
Study officials:
affiliation: Erasme University Hospital
name: Walter Feremans, MD, PhD
role: STUDY_CHAIR
References: