Clinical trial NCT02791373: Vinorelbine and Gemcitabine in Myeloma
Official title: A Randomized Evaluation of Vinorelbine Versus Gemcitabine for Mobilization of Peripheral Stem Cells in Myeloma Patients Undergoing Autologous Stem Cell Transplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Amyloidosis
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2016-06-06
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the efficacy of gemcitabine is comparable with the efficacy of the standard chemotherapy with vinorelbine for mobilization of autologous stem cells in myeloma patients

Detailed description: Mobilization and engraftment of autologous peripheral blood progenitor cells (PBPC) in newly diagnosed multiple myeloma (MM) or amyloidosis patients followed by high dose chemotherapy with PBPC support.

Eligible are symptomatic myeloma or amyloidosis patients after standard first-line induction treatment. Patients must be fit for subsequent consolidation with high-dose chemotherapy with melphalan with autologous stem cell support.

Chemotherapy with vinorelbine is given at a standard dose of 35mg/m2 i.v. at day 1 as an infusion over 10 minutes, on an ambulatory basis. Gemcitabine is given at the standard dose of 1250 mg/m2 i.v. in 500ml NaCl 0.9% (sodium chlorid) as an infusion over 30 minutes, on an ambulatory basis.

G-CSF (granulocyte-colony stimulating factor) is given at 60 Mio s.c./d for patients ≤ 69kg in two daily doses of 30 Mio 12 hours apart, at 78 Mio s.c./d for patients from 70kg to 89kg with 48 Mio given in the morning and 30 Mio given in the evening, and at 96 Mio s.c./d for patients ≥ 90kg in two daily doses of 48 Mio.

Patients will be randomized in a 1:1 ratio between vinorelbine and gemcitabine mobilization. Patients will be stratified according to (A) response to induction treatment (refractory/stable disease/partial response versus very good partial response/complete response) and (B) peripheral neuropathy present versus absent before mobilization.

The high dose chemotherapy supported by autologous stem cell transplantation is not part of the study treatment. Standard high dose melphalan (200 mg/m2) will be used as conditioning regimen. After transplantation, G-CSF will be given to subjects starting at day +6 until day +11 after PBPC re-infusion, at a dose of 30 Mio per day for patients ≤ 75kg, and of 48 Mio for patients \>75kg.

Planned accrual is chemotherapy with vinorelbine is given at a standard dose of 35mg/m2 i.v. at day 1 as an infusion over 10 minutes, on an ambulatory basis. Gemcitabine is given at the standard dose of 1250 mg/m2 i.v. in 500ml NaCl 0.9% as an infusion over 30 minutes, on an ambulatory basis.

G-CSF is given at 60 Mio s.c./d for patients ≤ 69kg in two daily doses of 30 Mio 12 hours apart, at 78 Mio s.c./d for patients from 70kg to 89kg with 48 Mio given in the morning and 30 Mio given in the evening, and at 96 Mio s.c./d for patients ≥ 90kg in two daily doses of 48 Mio.

Patients will be randomized in a 1:1 ratio between vinorelbine and gemcitabine mobilization. Patients will be stratified according to (A) response to induction treatment (refractory/stable disease/partial response versus very good partial response/complete response) and (B) peripheral neuropathy present versus absent before mobilization.

The high dose chemotherapy supported by autologous stem cell transplantation is not part of the study treatment. Standard high dose melphalan (200 mg/m2) will be used as conditioning regimen. After transplantation, G-CSF will be given to subjects starting at day +6 until day +11 after PBPC re-infusion, at a dose of 30 Mio per day for patients ≤ 75kg, and of 48 Mio for patients \>75kg.

Planed accrual of 136 patients in 42 months.

Eligibility criteria: Inclusion Criteria:

* Symptomatic myeloma or amyloidosis patients after standard first-line induction treatment. Patients must be fit for subsequent consolidation with high-dose chemotherapy with melphalan with autologous stem cell support.
* Standard induction chemotherapy comprises regimens including thalidomide, bortezomib, or lenalidomide (less than 5 cycles), alone or in combination with dexamethasone. Combinations of novel agents are allowed as well as induction with the VAD (vincristine, adriamycin and dexamethasone) regimen.
* Patient must be aged 18-75 years, with an ECOG (Eastern Cooperative Oncology Group) \< 3, and has given voluntary written informed consent.
* Patient has the following laboratory values at baseline:
* Platelets count \> 50 x 109/l without transfusion support within 7 days before the laboratory test.
* Absolute neutrophil count (ANC) \> 1.0 x 109/l without the use of colony stimulating factors.
* Creatinine-clearance \> 40 ml/min
* Negative pregnancy test (urine or serum) within 14 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement adequate measures (hormonal treatment p.o. or i.m., intra uterine surgical devices, or latex condoms) to avoid pregnancy during study treatment and for additional 12 months. No pregnant or lactating patients are allowed.

Exclusion Criteria:

* Patients with more than 4 cycles of chemotherapy with lenalidomide.
* Patients not fit for autologous stem cell transplantation
* Patients with other serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery.
* Subject is currently enrolled in another investigational trial or is receiving other investigational agent(s).

Primary outcomes:
measure: CD34+ (cluster of differentiation 34) peripheral blood stem cells
timeFrame: Day 8
Secondary outcomes:
measure: Rate of peripheral neuropathy
timeFrame: Between 15 and 30 days
measure: Severity of peripheral neuropathy
timeFrame: Between 15 and 30 days
measure: Hematologic recovery
timeFrame: Between 15 and 30 days
measure: Minimal residual disease in the peripheral blood
timeFrame: Day 8
measure: Need to use the stem cell releasing compound Plerixafor
timeFrame: Day 8
measure: Response Rate
timeFrame: Between 15 and 30 days
Other outcomes:
Locations:
city: Berne
country: Switzerland
facility: Department for Medical Oncology; University Hospital/Inselspital
Study officials:
affiliation: Inselspital , University Hospital Berne
name: Thomas Pabst, MD
role: STUDY_CHAIR
References:
citation: Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996 Jul 11;335(2):91-7. doi: 10.1056/NEJM199607113350204.