Carfilzomib, Cyclophosphamide, Dexamethasone in Transplant Eligible Newly Diagnosed High-risk Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Study of Carfilzomib in Transplant Eligible Newly Diagnosed High-risk Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02217163
• Other study ID #: SGHMM1
• Status: Completed
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: October 2020

Study information

• Verified date: October 2020
• Source: Singapore General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with high risk multiple myeloma have shorter remission periods and reduced overall survival. Prognostic significance of minimal residual disease negative remission is being highlighted in many of the newer studies.

The current phase 2 study investigates the combination of carfilzomib together with cyclophosphamide and dexamethasone in patients with high risk multiple myeloma in younger transplant-eligible patients.

Description:

Carfilzomib is administered over 30 minutes as an infusion. For cycle 1 only, Carfilzomib is administered at 20mg/m2 IV on days 1 and 2, followed by escalation to 36 mg/m2 on days 8,9,15 and 16 on a 28 day cycle. Patients who tolerate 36 mg/m2 dose are kept at this dose for the subsequent cycles on Days 1, 2, 8, 9, 15, 16 on a 28 day cycle. Dose and schedule modifications for intolerable side effects are detailed in the protocol. Additionally Cyclophosphamide is given a fixed dose of 500mg once per week orally, along with dexamethasone, given on the days of Carfilzomib administration, 30 minutes to 4 hours prior to Carfilzomib. Patients will undergo blood tests weekly and serum protein electrophoresis every 4 weeks during treatment. Within completion of 5 cycles of treatment, patients would undergo stem cell collection using chemotherapy and GCSF mobilization. After completion of 6 cycles of treatment, autologous bone marrow transplantation will be performed. Three months following bone marrow transplantation, subjects will undergo further 2 consolidation cycles. After consolidation, subjects will undergo disease assessment by blood and subjects who are in CR will undergo bone marrow investigations and MRD analysis MPFC. Patients who achieve MRD negativity by MPFC will be managed expectantly by watch and wait. Patients who are MRD positive at this stage will receive maintenance for 2 years or till disease progression. Follow up would extend till a minimum of 2 years from completion of the study. At the end of 2 years post maintenance or expectant monitoring, subjects who are in CR will undergo disease assessment by blood and bone marrow investigations and MRD analysis MPFC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2020
• Est. primary completion date: October 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Newly diagnosed Multiple Myeloma AND Transplant eligible AND

2. High Risk as defined by:

• International Staging System 3 OR

• FISH abnormality of t(4,14), t(14;16), 17p deletion or 1q amp

3. Patients must have evaluable myeloma, with at least one of the following (Assessed within 28 days of commencing the study)

• Serum M protein >/= 0.5g/dL or

• Urine M protein >200mg/24hr

• Serum free light chains >100mg/mL (involved light chain) and abnormal k/l ratio

• For IgA patients who have no other means of measurement of disease, sIgA level >0.75g/dL

Exclusion Criteria:

1. Relapsed Myeloma

2. Non transplant eligible patient.

3. IgM subtype Myeloma

4. POEMS syndrome

5. Amyloidosis

6. Waldenstroms Macroglobulinemia

7. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days of randomization (Limited site radiation allowed).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib, , Cyclophosphamide, Dexamethasone
Carfilzomib is administered intraveneously over 30 minutes. For cycle 1 only, Carfilzomib is administered at 20mg/m2 on Day 1 and 2, dose will be escalated to 36mg/m2 on Day 8,9,15 and 16 of the 28-days cycle. Patients who tolerate the 36mg/m2 dose are kept at this dose for the subsequent cycles on Day 1,2,8,9,15,16 on a 28 days cycle. Cyclophosphamide is given at a fixed dose of 500mg once per week orally, along with dexamethasone which is given on the days of Carfilzomib administration, 30 minutes to 4 hours prior to Carfilzomib infusion.

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Singapore General Hospital

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	To study the progression free survival (PFS) in patients with newly diagnosed high risk multiple myeloma treated with Carfilzomib, Cyclophosphamide and Dexamethasone, followed by autologous bone marrow transplantation.	2 years
Secondary	Minimal residual disease negativity	Minimal residual disease burden at different time points, as assessed by multi parameter flow cytometry (MPFC).	2 years
Secondary	Overall Survival (OS)	OS is defined as the time from entering study to death of any cause.	2 years