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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cohort 1: Carfilzomib 15 mg/m2; Drug: Cohort 2: Carfilzomib 20 mg/m2; Drug: Cohort 2b: Carfilzomib 20 mg/m2; Drug: Cohort 3b: Carfilzomib 27 mg/m2

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1: Carfilzomib 15 mg/m2; Carfilzomib 15 mg/m2 on days -2, -1, +5, and +6 IV over 10 minutes.	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; Other Names: Carfilzomib - Kyprolis; Bendamustine - Treanda; Melphalan - Alkeran
Active Comparator: Cohort 2: Carfilzomib 20 mg/m2; Carfilzomib 20 mg/m2 on days -2, -1, +5, and +6 IV over 10 minutes.	Drug: 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; Other Names: Carfilzomib - Kyprolis; Bendamustine - Treanda; Melphalan - Alkeran
Active Comparator: Cohort 2b: Carfilzomib 20 mg/m2; Carfilzomib 20 mg/m2 on days -2, -1 and +5 IV over 10 minutes.	Drug: 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; Other Names: Carfilzomib - Kyprolis; Bendamustine - Treanda; Melphalan - Alkeran
Active Comparator: Cohort 3: Carfilzomib 27mgm2; Carfilzomib 27 mg/m2 on days -2, -1 and +5 IV over 10 minutes.	Drug: 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; Other Names: Carfilzomib - Kyprolis; Bendamustine - Treanda; Melphalan - Alkeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absence of 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil 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. 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.
Platelet Engraftment	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.	Assessed daily (while inpatient) through clinical and laboratory examinations up to 90 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Investigators: Principal Investigator: Muneer H Abidi, MD, Spectrum Health Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 23, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimated): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Bendamustine Hydrochloride; Melphalan
• Other Study ID Numbers: 2014-067