Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02288741
Other study ID # WiSP_AM71
Secondary ID protocol version
Status Completed
Phase Phase 3
First received October 23, 2014
Last updated November 6, 2014
Start date August 2001
Est. completion date September 2012

Study information

Verified date November 2014
Source WiSP Wissenschaftlicher Service Pharma GmbH
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices
Study type Interventional

Clinical Trial Summary

Patients 60 to 70 years of age with newly diagnosed multiple myeloma were prospectively randomized between 4 cycles of anthracycline/dexamethasone-based induction chemotherapy (A1) or only 2 x 4 days of dexamethasone (A2). A reference arm included patients who could not be randomized (B). Tandem melphalan 140 mg/m² (MEL140) with autologous transplantation was scheduled for all patients.


Description:

In arm A1, patients received 4 cycles of conventional induction therapy with anthracycline/dexamethasone-based regimens. Specified in the protocol were vincristine/doxorubicin/dexamethasone (VAD), idarubicin/dexamethasone (ID) and cyclophosphamide/doxorubicin/dexamethasone (CAD). In arm A2, patients were planned to receive only dexamethasone 40 mg orally on days 1-4 and 8-11 for symptom control before stem cell mobilization. For the patients in arm B, a maximum of 6 cycles of induction chemotherapy was allowed. Following this, the treatment was identical for all patients. For stem cell mobilization, an age-adjusted IEV-regimen with granulocyte-colony stimulating factor (G-CSF) was recommended. The target dose for stem cell collection was 6 x 10E+6 CD34 (cluster of differentiation 34)-positive cells/kg (2 transplants and one back-up). The standard dose for each transplantation was 2 x 10E+6 CD34-positive cells/kg. High-dose melphalan at a total dose of 140 mg/m² (MEL140) was given in two doses of 70 mg/m² on days -3 and -2. Stem cell transplantation (SCT) was performed on day 0. A second MEL140 course was planned two months after the first. Regular bisphosphonate treatment was recommended.


Recruitment information / eligibility

Status Completed
Enrollment 549
Est. completion date September 2012
Est. primary completion date September 2012
Accepts healthy volunteers No
Gender Both
Age group 60 Years to 70 Years
Eligibility Inclusion Criteria:

- Histological confirmed multiple myeloma stage II or III according to the classification of Salmon and Durie

- Aged between 60 and 70 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Signed and dated written informed consent

- No previous chemotherapy or not more than one cycle in total or previous chemotherapy of more than one cycle if paused for at least 6 months and not more than six cycles in total (arm A1 and A2 only)

- Ongoing primary chemotherapy of two to maximum six cycles (arm B only)

Exclusion Criteria:

- Multiple myeloma stage I according to the classification of Salmon and Durie without need of any therapy

- Aged under 60 or over 70 years

- ECOG performance status >2

- Previous chemotherapy of more than six cycles

- Informed consent missing

- Myocardial infarction within the last six months

- Cardiac dysrhythmia stage IV b according to the classification of Lown

- Heart failure >NYHA II according to the classification of the New York Heart Association (NYHA), left ventricular ejection fraction <50% in ECG

- Severe restrictive or obstructive pulmonary disease (diffusing capacity <60% under normal)

- Renal insufficiency including a serum creatinine level >2mg/dl if not caused by multiple myeloma and reversible

- Liver diseases combined with an elevation of transaminases and of bilirubin of three times above normal

- Severe infections (HIV, hepatitis B/C, syphilis etc. )

- Severe psychiatric disease

- Other not curative treated malignant tumor within the last five years

- Concurrent participation in other clinical studies

- Other not curative treated malignant tumor within the last five years

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Anthracycline/dexamethasone-based induction chemotherapy
4 cycles of anthracycline/dexamethasone-based chemotherapy
Dexamethasone for control of symptoms
2 x 4 days of dexamethasone (day 1-4 and day 8-11: 40mg)
Tumor-reduction chemotherapy and stem cell mobilization
Ifosfamide (day 1-3: 1.900mg/m² iv), epirubicin (day 1: 75 mg/m² iv), etoposide (day 1-3: 120 mg/m² iv) and G-CSF (day 5 until end of apheresis: 5µg/kg sc)
Procedure:
Stem cell apheresis
stem cell apheresis in peripheral blood, sought amount of CD34-cells: 6 * 10E6/kg
Drug:
Tandem high-dose chemotherapy (melphalan)
Two cycles of high-dose melphalan (day -3 and day -2: 70mg/m²)
Procedure:
Autologous peripheral blood stem cell transplantation
Two infusions of collected stem cells (day 0: 2*10E6 CD34-cell/kg per transplantation)

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
WiSP Wissenschaftlicher Service Pharma GmbH

References & Publications (5)

Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. — View Citation

Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. — View Citation

Clark AD, Douglas KW, Mitchell LD, McQuaker IG, Parker AN, Tansey PJ, Franklin IM, Cook G. Dose escalation therapy in previously untreated patients with multiple myeloma following Z-Dex induction treatment. Br J Haematol. 2002 Jun;117(3):605-12. Erratum in: Br J Haematol 2002 Sep;118(4):1201. — View Citation

Straka C, Hebart H, Adler-Reichel S, Werding N, Emmerich B, Einsele H. Blood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma. Oncology. 2003;65 Suppl 2:94-8. — View Citation

Szelényi H, Kreuser ED, Keilholz U, Menssen HD, Keitel-Wittig C, Siehl J, Knauf W, Thiel E. Cyclophosphamide, adriamycin and dexamethasone (CAD) is a highly effective therapy for patients with advanced multiple myeloma. Ann Oncol. 2001 Jan;12(1):105-8. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Event free survival Calculated according to the method of Kaplan and Meier From randomization to 10 years follow up No
Secondary Overall survival Calculated according to the method of Kaplan and Meier From randomization to 10 years follow up No
Secondary Rate of remission (Evaluation of the overall response rate) Evaluation of the overall response rate. Overall repose is defined as complete response + partial response. The definition of remission followed the criteria of Bladé. After last therapy to at least 6 weeks thereafter No
Secondary Quality of remission (Evaluation of the best response) Evaluation of the best response. Response is evaluated after induction therapy, tumor-reduction chemotherapy and stem cell mobilization and each high-dose chemotherapy. The definition of remission followed the criteria of Bladé. After last therapy to at least 6 weeks thereafter No
Secondary Short and long time toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE) Examination of the maximum grade of toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE) From randomization until 2 years after last therapy Yes
Secondary Cytogenetic examination (Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis.) Examination of cytogenetic abnormalities wich are of major importance to define longer or shorter survival. Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis. From randomization to 10 years follow up No
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1