Phase I: Melphalan, Bendamustine and Carfilzomib for Autologous Transplant in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase I Study of Melphalan, Bendamustine, and Carfilzomib for Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02148913
• Other study ID #: 2014-067
• Status: Completed
• Phase: Phase 1
• Start date: June 2014
• Est. completion date: December 2018

Study information

• Verified date: April 2019
• Source: Spectrum Health Hospitals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase I clinical trial. Patients with a diagnosis of multiple myeloma undergoing autologous transplantation will receive a preparative regimen of melphalan, bendamustine, and carfilzomib. We hypothesize that the addition of carfilzomib to a conditioning regimen of melphalan and bendamustine in the setting of autologous transplantation for multiple myeloma is feasible and safe.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of multiple myeloma

• At least 2 x 106 CD34+ cells/kg have been collected from the patient and cryopreserved for ASCT

• Greater than 18 years

• Karnofsky score greater than 70%

• No evidence of progressive bacterial, viral, or fungal infection

• Absolute neutrophil count above 1000

• Platelet count above 50,000

• Hemoglobin above 8 g/dL

• Creatinine clearance greater than 50 mL/min

• Total bilirubin, ALT, and AST less than 2 x the upper limit of normal

• Alkaline phosphatase less than or equal to 250 IU/L

• Left Ventricular Ejection Fraction (LVEF) greater than or equal to 45%

• Adjusted Carbon Monoxide Diffusing Capacity (DLCO) greater than or equal to 60%

• Negative HIV serology

• Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)

• Patients with a pre-transplant disease status consistent with a very good partial response (VGPR), partial response (PR), stable disease (SD), progressive disease (PD), or relapse from complete remission (CR).

Exclusion Criteria:

• Patients who are refractory to carfilzomib. Refractory is defined as disease progression while on carfilzomib therapy after receiving at least two cycles of treatment.

• Patients with a complete response (CR) (including near CR and stringent CR) to conventional induction therapy and proceeding to transplantation.

• Pregnant or nursing females or women of reproductive capability who are unwilling to use effective contraception. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row.

• Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (ie, post-vasectomy).

• Patient with Grade 2 peripheral neuropathy

• Inability to provide informed consent

• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

• Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.

• Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments.

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• Diagnosed or treated for another malignancy within 3 years of enrollment (with the exception of non-melanoma skin cancer).

• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.

• Prisoner

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Cohort 1: Carfilzomib 15 mg/m2
Carfilzomib 20 mg/m2 on days -29, -28, -22, -21, -15, and -14 Bendamustine 120 mg/m2 on day -2 and 100 mg/m2 day -1 Melphalan 100 mg/m2 on day -2 and day -1 Carfilzomib 15 mg/m2 on day -2, -1, + 5 and +6
• Cohort 2: Carfilzomib 20 mg/m2
Carfilzomib 20 mg/m2 on days -29, -28, -22, -21, -15, and -14 Bendamustine 120 mg/m2 on day -2 and 100 mg/m2 day -1 Melphalan 100 mg/m2 on day -2 and day -1 Carfilzomib 20 mg/m2 on day -2, -1, + 5 and +6
• Cohort 2b: Carfilzomib 20 mg/m2
Carfilzomib 20 mg/m2 on days -29, -28, -22, -21, -15, and -14 Bendamustine 120 mg/m2 on day -2 and 100 mg/m2 day -1 Melphalan 140 mg/m2 on day -1 Carfilzomib 20 mg/m2 on day -2, -1 and + 5
• Cohort 3b: Carfilzomib 27 mg/m2
Carfilzomib 20 mg/m2 on days -29, -28, -22, -21, -15, and -14 Bendamustine 120 mg/m2 on day -2 and 100 mg/m2 day -1 Melphalan 140 mg/m2 on day -1 Carfilzomib 27 mg/m2 on day -2, -1 and + 5

Locations

Country	Name	City	State
United States	Spectrum Health	Grand Rapids	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Health Hospitals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Response Rate	Find the response rate of the combination of melphalan, bendamustine, and carfilzomib as a conditioning regimen in patients with multiple myeloma undergoing autologous transplantation.	Disease assessment at day +100, +180, and +365 (+/- 7 days).
Primary	Dose Limiting Toxicity	An absence of neutrophil engraftment by Day +22, absence of platelet engraftment by Day +35, and any grade 4 GI toxicity or any >/= grade 3 non-hematologic toxicity as defined by the common toxicity criteria, which is deemed by the DSMB as probably related to the study protocol.	Assessed daily (while inpatient) through clinical and laboratory examinations up to 90 days.
Secondary	Engraftment	Engraftment of Neutrophils: ANC recovery is defined as an absolute neutrophil count (ANC) of = 0.5 x 109/L for three consecutive laboratory values obtained on different days. The day used as neutrophil engraftment is the date of the first of three laboratory values.; Engraftment of Platelets: Platelet engraftment is defined as a platelet count = 20 x 109/L for 3 consecutive measurements obtained on different days. The patient must not have received a platelet infusion for seven consecutive days prior to the first day being considered. The day used as platelet engraftment is the date of the first of three laboratory values.; Graft Failure: Graft failure includes failure to achieve neutrophil engraftment by day 22.	Assessed daily (while inpatient) through clinical and laboratory examinations up to 90 days.