NCT02858999

Brief Summary

Plasma cell leukaemia is a rare variety of multiple myeloma with a poor prognosis. Plasma cell leukaemia is defined as: at least 2,000 circulating plasma cells per µL for a blood leukocyte count higher than 10,000/µL or 20% of plasma cells for a leukocyte count less than 10,000/µL. Plasma cell leukaemia can be either primary, when it constitutes the first manifestation of the disease, or secondary in the setting of relapsed/refractory multiple myeloma. Primary plasma cell leukaemia (PPL) is a rare disease, representing only 1 to 2% of all cases of multiple myelomas at diagnosis. As the annual incidence of multiple myeloma in France is about 4,000 new cases, an estimated 40 to 80 new cases of PPL would be observed each year. Few data are currently available in the literature concerning the pathophysiology and therapeutic management of PPL, and are derived from retrospective series based small numbers of patients. The prognosis of PPL in response to conventional chemotherapy remains poor with a median survival of 7 to 14 months. However, longer survivals have been obtained with intensive therapy and haematopoietic stem cell transplantation (allogeneic or autologous HSCT). The investigators propose to perform a prospective study of the management of patients with PPL under the age of 70 years, in combination with a laboratory study: 12 weeks of induction chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles. Peripheral blood stem cell collection after mobilization by G-CSF will be performed after high-dose Cyclophosphamide chemotherapy. Autologous HSCT conditioned by high-dose Melphalan will be performed during the following month for all responding patients. During the 3 months after this first autologous HSCT, allogeneic HSCT with attenuated conditioning will be proposed in patients under the age of 66 years in complete remission with a suitable donor, and another systematic autologous HSCT will be proposed in all other patients. For all patients not treated by allogeneic HSCT, consolidation/maintenance therapy will be performed 3 months after the second autologous HSCT: 4 quarterly consolidations with Bortezomib-Lenalidomide-Dexamethasone (VRD) with maintenance by 2 months of Lenalidomide between these cycles, for a total duration of one year. The laboratory assessment will consist of blood and bone marrow samples systematically obtained at diagnosis for plasma cell phenotyping by cytometry, cytogenetics, FISH, study of the gene expression profile and SNParray. A DNA bank and plasma bank will be constituted. The investigators also propose to study residual disease by cytometry (after the first autologous HSCT, before and at the end of the consolidation/maintenance phase), as it increasingly appears to have a major impact on survival in multiple myeloma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2 multiple-myeloma

Timeline
Completed

Started Jan 2010

Typical duration for phase_2 multiple-myeloma

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2010

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 4, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 8, 2016

Completed
24 days until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
Last Updated

September 19, 2025

Status Verified

September 1, 2025

Enrollment Period

6.5 years

First QC Date

August 4, 2016

Last Update Submit

September 16, 2025

Conditions

Keywords

primary plasma cell leukaemiatreatment

Outcome Measures

Primary Outcomes (1)

  • Disease-free survival

    3 years

Study Arms (1)

treatment

EXPERIMENTAL

12 weeks of induction chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles PAD-VCD

Drug: PAD-VCD

Interventions

12 weeks of induction chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles

treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient with primary plasma cell leukaemia corresponding to the International Myeloma Working Group definition.
  • Patient not previously treated apart from a short course of corticosteroid therapy (dexamethasone 40 mg/day for 4 days).
  • Age ≥ 18 years and \< 70 years.
  • Patient able to provide signed informed consent.
  • Effective contraception when justified (oral contraception/protected intercourse).

You may not qualify if:

  • Consent not obtained.
  • Patient under judicial protection, or permanent or temporary guardianship.
  • Previously treated multiple myeloma, secondary plasma cell leukaemia.
  • ECOG performance status \> 2.
  • History of severe psychiatric illness, severe renal failure not attributable to PPL, heart failure (ejection fraction \< 40%), bilirubin \> 3N, transaminases or gamma GT \> 4N.
  • Peripheral neuropathy \> NCI grade 2.
  • Contraindication to high-dose corticosteroids, cyclophosphamide and anthracyclines.
  • Hypersensitivity to bortezomib or lenalidomide.
  • Pregnant woman or nursing mothers.
  • Malignant disease except for basal cell carcinoma or cervical carcinoma in situ.
  • Positive HIV serology; active hepatitis B or C.
  • Patient not covered by French national health insurance.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

CH Pays d'Aix

Aix-en-Provence, 13616, France

Location

CHU Amiens

Amiens, 80054, France

Location

CHU Besançon

Besançon, 25030, France

Location

CHU Caen

Caen, 14033, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, 63003, France

Location

CHU Dijon

Dijon, 21034, France

Location

CH Dunkerque

Dunkirk, 59385, France

Location

CHRU Lille

Lille, 59037, France

Location

Hospices Civils de Lyon

Lyon, 69229, France

Location

CHU Nancy

Nancy, 54035, France

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Nice

Nice, 06003, France

Location

AP-HP

Paris, 75004, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

CHU Rennes

Rennes, 35033, France

Location

CHU Strasbourg

Strasbourg, 67091, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

CHU Tours

Tours, 37044, France

Location

Related Publications (1)

  • Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myelome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. doi: 10.1200/JCO.2015.63.1929. Epub 2016 Apr 25.

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Bruno ROYER, PhD

    CHU Amiens

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2016

First Posted

August 8, 2016

Study Start

January 1, 2010

Primary Completion

July 1, 2016

Study Completion

September 1, 2016

Last Updated

September 19, 2025

Record last verified: 2025-09

Locations