PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma

NCT01220375 | Completed Phase 2 DMC

• 4 other identifiers: 236/092010DR205210-CPRS-0011795
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

High-dose chemotherapy with autologous stem cell support is the current standard procedure in the first-line treatment in younger patients with myeloma fit for intensive treatment. Current practice in Switzerland for stem cell mobilization is the combination of chemotherapy and G-CSF stimulation in myeloma patients fit for high-dose chemotherapy with melphalan and autologous stem cell transplant. In this trial the intravenous application of Plerixafor is being investigated in respect of the capability of the mobilization of stem cells from the bone marrow into the peripheral blood. In contrast to the twice daily application of G-CSF (eg. Neupogen) for several days, Plerixafor has to be injected just one-time.

Conditions

Myeloma

Keywords

Mobilization of autologous peripheral blood progenitor cells PBPC; Autologous stem cell mobilization; Multiple Myeloma; Plerixafor

Outcome Measures

Primary Outcomes (1)

• Number of patients from whom ≥ 6 million CD34+ peripheral blood stem cells/kg are harvested in a maximum of 2 days

  day 8 (and 9, if necessary) / 2 days after G-CSF

Secondary Outcomes (3)

• Incidence and severity of adverse events during and after the use of plerixafor

  15 days

• Proportion of patients with engraftment of PBPC defined as an ANC recovery of ≥ 0.5 x 109/L for 3 consecutive days and a platelet recovery of ≥ 20 x 109/L in the absence of platelet transfusion for at least 7 days

  21 months

• Comparison of costs for mobilization of PBPC with vinorelbine and plerixafor versus the costs for mobilization with vinorelbine and filgrastim and versus the costs for mobilization with vinorelbine and pegfilgrastim

  21 Months

Study Arms (1)

1

EXPERIMENTAL

Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.

Drug: Vinorelbine, G-CSF, & Plerixafor; Drug: Vinorelbine and Plerixafor; Drug: G-CSF and Plerixafor; Drug: Vinorelbine & Plerixafor on day when CD34 count is at least 15'000 CD34+ cells/ml of peripheral blood

Interventions

Vinorelbine, G-CSF, & Plerixafor DRUG

Patients 1-10 receive 35 mg/m2 vinorelbine i.v. on day 1, G-CSF divided in two daily doses from day 4 until collection of stem cells, and plerixafor as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. Stem cell collection is initiated 4 hours later (at 12:00 PM) at day 8, if at least 20 X 103 of CD34+ cells / ml peripheral blood are detected.

1

Vinorelbine and Plerixafor DRUG

Patients 11-20 receive 35 mg/m2 vinorelbine i.v. on day 1 and plerixafor as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. No G-CSF will be administered. Stem cell collection is initiated 4 hours later (at 12:00 PM) at day 8, if at least 20 X 103 of CD34+ cells / ml peripheral blood are detected.

1

G-CSF and Plerixafor DRUG

Patients 21-30 receive G-CSF divided in two daily doses from day 4 until collection of stem cells, and plerixafor as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. No chemotherapy with vinorelbine will be gine on day 1. Stem cell collection is initiated 4 hours later (at 12:00 PM) at day 8, if at least 20 X 103 of CD34+ cells / ml peripheral blood are detected.

1

Vinorelbine & Plerixafor on day when CD34 count is at least 15'000 CD34+ cells/ml of peripheral blood DRUG

Patients 31-40 receive 35 mg/m2 vinorelbine i.v. on day 1 and plerixafor as an i.v. application at 08:00 AM, on the first day on which the CD34 count has risen to at least 15'000 CD34+ cells/ml of peripheral blood. Stem cell collection is initiated 4 hours later (at 12:00 PM) on this day. No G-CSF will be administered.

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic stage I or stage II and III myeloma patients after standard first-line non-melphalan containing 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 (up to 4 cycles), alone or in combination with dexamethasone. Combinations of novel agents are allowed as well as induction with the VAD regimen.
• Patients must have achieved at least a partial response according to the Bladé criteria after induction chemotherapy.
• Patient must be aged 18-70 years, with an ECOG \< 2 and has given voluntary written informed consent.
• 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.
• Corrected serum calcium \< 3 mmol/L.
• Aspartate transaminase (AST) \<= 1.5 x ULN.
• Alanine transaminase (ALT) \<= 1.5 x ULN.
• Total bilirubin \<= 2 x ULN.
• Creatinin-clearance \>= 50 ml/min.
• Negative pregnancy test within 14 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement adequate measures to avoid pregnancy during study treatment and for additional 12 months. No pregnant or lactating patients are allowed.

You may not qualify if:

• Patients previously treated with melphalan or extensive radiotherapy to the bone marrow.
• Patients with more than 4 cycles of chemotherapy with Lenalidomide.
• Patients not fit for autologous stem cell transplantation.
• Patient receiving colony stimulating factors.
• Patient underwent plasmaphereses within 4 weeks before enrolment.
• Patient had major surgery within 4 weeks before enrolment.
• Patient has 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.
• Sero-positive for HIV antibody.
• Patient known to be hepatitis B surface antigen positive or who has an active hepatitis C infection.
• Patient has an active systemic infection requiring treatment.
• Female patient is pregnant or breast feeding.
• Compromised renal function as evidenced by measured or calculated creatinine clearance \<= 50 ml/min.
• Subject is currently enrolled in, or has not yet completed at least 30 days since ending another investigational device or drug trial or is receiving other investigational agent.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Dep. of Medical Oncology, Bern University Hospital

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Vinorelbine; Granulocyte Colony-Stimulating Factor; plerixafor

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Thomas Pabst, Associate Professor

  Dep. Medical Oncology, Bern University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 11, 2010
• First Posted: October 13, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: October 1, 2013
• Last Updated: April 17, 2014

Record last verified: 2014-04

Locations

CH (1)