Carfilzomib, Cyclophosphamide, Dexamethasone in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Carfilzomib and Dexamethasone in Combination With Cyclophosphamide vs. Carfilzomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: a Phase II Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03336073
• Other study ID #: GEM-KyCyDex
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: December 2024

Study information

• Verified date: September 2022
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open label, phase II randomized controlled study that will evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in R/R MM patients.

For this purpose, R/R MM patients that have received 1-3 prior lines of therapy, and who are not primary refractory or refractory to proteasome inhibitors will be randomized to receive:

• Experimental arm: carfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15, dexamethasone by mouth (po) at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16 and cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15, in 28 days cycles; or

• Control arm: the same treatment but without cyclophosphamide.

Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.

Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.

Treatment will be continued until progression, unacceptable toxicity or investigator or patient decision.

Description:

Treatment will consist of 28-days cycles with:

• Arm 1 (experimental arm):

• Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8 and 15.

• Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.

• Cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15

• Arm 2 (control arm):

• Carfilzomib administered iv at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) iv on days 1, 8, and 15.

• Dexamethasone at a dose of 20 mg po (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16.

Once the first 12 cycles are administered, treatment will be administered on days 1 and 15 of each cycle and the visit and doses on day 8 will be omitted in both study arms.

Patients older than 75 years will receive in both arms carfilzomib at a dose of 56 mg/m2 (20 mg/m2 only in the first infusion) during the cycles 1 and 2. If tolerability is acceptable, the dose could be increased up to 70 mg/m2 since the cycle 3.

Treatments will be administered until progressive disease (PD) or unacceptable toxicity. Carfilzomib and cyclophosphamide will be provided by the sponsor. Dexamethasone may be utilized per a site's standard practice and will not be provided by the sponsor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 199
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years.

2. Performance status (ECOG) <2.

3. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

4. Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

5. Patients previously diagnosed with MM according to the IMWG criteria (Lancet Oncology 2014) that after previous treatment with 1-3 regimens require therapy due to a relapse/progression of the disease.

6. Patients must have measurable disease, defined as follows:

• Serum monoclonal protein = 0.5 g/L, or

• Urine light-chain excretion of = 0.2g /24 hours, or

• Abnormal ratio of serum free light chains (FLCs) plus involved FLC level =100 mg/L.

Exclusion Criteria:

1. Primary refractory patients defined as not having achieved at least a PR with a prior therapy.

2. Refractoriness to prior proteasome inhibitor therapies, defined as not having achieved at least MR or having progressed under treatment or in the first 60 days after the last dose of the proteasome inhibitor.

3. Biochemical and haematological abnormalities as specified below:

• Hemoglobin < 8.0 g/dL.

• Platelet count <75x109/L without previous platelet transfusions in the last 7 days. If bone marrow infiltration is greater than 50%, a platelet count of =50x109/L is required.

• Absolute neutrophil count (ANC) < 0.75 x109/L without G-CSF support in the last 7 days.

• Aspartate transaminase (AST): > 2.5 times the upper limit of normal.

• Alanine transaminase (ALT): > 2.5 times the upper limit of normal.

• Calculated or measured creatinine clearance: <30 mL/min (calculated from the Cockcroft and Gault formula, specified in Appendix C).

4. Left ventricle ejection fraction < 50%.

5. Absence of recovery from any significant non-haematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.

6. Pregnant or breastfeeding women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, and oral contraception).

7. Previous history of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site).

8. Other relevant diseases or adverse clinical conditions:

• Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.

• Uncontrolled arterial hypertension or cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months).

• History of significant neurological or psychiatric disorders.

• Active infection

• Significant non-neoplastic liver disease (e.g. cirrhosis, active chronic hepatitis).

9. Patient is known to be human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or to suffer active hepatitis C infection

10. The patient has received concomitant anti-myeloma therapy within 14 days prior to Day 1 of Cycle 1.

11. Limit to the patient's ability to comply with the treatment or follow-up protocol.

12. Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
carfilzomib at a dose of 70 mg/m2 (20 mg/m2 only in the first infusion) intravenously (iv) on days 1, 8, and 15
• Dexamethasone
dexamethasone oral at a dose of 20 mg (10 mg for patients >75 years) days 1, 2, 8, 9, 15 and 16
• cyclophosphamide
cyclophosphamide at a dose of 300 mg/m2 iv on days 1, 8 and 15

Locations

Country	Name	City	State
Spain	H.Universitari Germans Trias I Pujol de Badalona	Barcelona
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Ico L'Hospitalet	Barcelona
Spain	Complejo Hospitalario de Cáceres	Cáceres
Spain	Hospital de Cabueñes	Gijón
Spain	Centro Hospitalario Universitario de Granada	Granada
Spain	Hospital de León	León
Spain	H. 12 de Octubre	Madrid
Spain	H. Ramón y Cajal	Madrid
Spain	Hospital Sanchinarro	Madrid
Spain	Hospital Costa del Sol	Málaga
Spain	Hospital Universitario Morales Meseguer	Murcia
Spain	Hospital Virgn de la Arrixaca	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital de Son Llàtzer	Palma De Mallorca
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Santiago	Santiago De Compostela
Spain	Hospital de Segovia	Segovia
Spain	Complejo Hospitalario Regional Virgen Del Rocío	Sevilla
Spain	Hospital Universitario de Canarias	Tenerife	Islas Canarias
Spain	Hospital de Toledo	Toledo
Spain	Hospital Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (28)

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	PFS is defined as the number of months from randomization to the disease progression or death due to any cause, whichever occurs first. The disease outcome determined will be the primary data source for the final PFS analysis.	36 months
Secondary	Safety of carfilzomib, dexamethasone and cyclophosphamide in number of participants with treatment-related adverse events as assessed by CTCAE v4.0	the safety as determined by the incidence of clinical and laboratory toxicities	2 years
Secondary	Efficacy of carfilzomib, dexamethasone and cyclophosphamide in number and rate of responses obtained	Evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in terms of rate of response in multiple myeloma (MM) patients.	2 years
Secondary	Time-to progression (TTP)	Duration from randomization to disease progression, with deaths due to causes other than progression censored.	36 months
Secondary	Overall Survival (OS)	Duration from the date of randomization until the date of death. The patients lost to follow-up will be censored at the date of the last visit.	36 months
Secondary	Efficacy of carfilzomib, dexamethasone and cyclophosphamide in rate of achievement of immunophenotypic CR	Evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in terms of achievement of immunophenotypic CR in multiple myeloma (MM) patients.	2 years