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

NCT ID: NCT02217163

Last Updated: 2020-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2020-10-31

Brief 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.

Detailed 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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

The combination therapy of Carfilzomib, cyclophosphamide and dexamethasone (KCyd) will be used to treat eligible patients for up to 6 cycles.This will be followed by an autologous bone marrow transplantation and 2 further consolidation cycles of KCyd. Depending on their disease response, patients will be managed expectantly or be started on maintenance.

Group Type: EXPERIMENTAL

Carfilzomib, , Cyclophosphamide, Dexamethasone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Kyprolis

Eligibility Criteria

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).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chandramouli Nagarajan, MBBS

Role: PRINCIPAL_INVESTIGATOR

Singapore General Hospital

Locations

National University Hospital

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Countries

Singapore

Other Identifiers

SGHMM1

Identifier Type: -

Identifier Source: org_study_id