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

NCT02148913 | Completed Phase 1 Results DMC

• 1 other identifier: 2014-067
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Neutrophil Engraftment

  Assessed daily (while inpatient) through clinical and laboratory examinations up to 90 days.

• Platelet Engraftment

  Assessed daily (while inpatient) through clinical and laboratory examinations up to 90 days.

Other Outcomes (1)

• Response Rate

  Disease assessment at day +100, +180, and +365 (+/- 7 days).

Study Arms (4)

Cohort 1: Carfilzomib 15 mg/m2

ACTIVE COMPARATOR

Carfilzomib 15 mg/m2 on days -2, -1, +5, and +6 IV over 10 minutes.

Drug: Cohort 1: Carfilzomib 15 mg/m2

Cohort 2: Carfilzomib 20 mg/m2

ACTIVE COMPARATOR

Carfilzomib 20 mg/m2 on days -2, -1, +5, and +6 IV over 10 minutes.

Drug: Cohort 2: Carfilzomib 20 mg/m2

Cohort 2b: Carfilzomib 20 mg/m2

ACTIVE COMPARATOR

Carfilzomib 20 mg/m2 on days -2, -1 and +5 IV over 10 minutes.

Drug: Cohort 2b: Carfilzomib 20 mg/m2

Cohort 3: Carfilzomib 27mgm2

ACTIVE COMPARATOR

Carfilzomib 27 mg/m2 on days -2, -1 and +5 IV over 10 minutes.

Drug: Cohort 3b: Carfilzomib 27 mg/m2

Interventions

Cohort 3b: Carfilzomib 27 mg/m2 DRUG

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

Also known as: Carfilzomib - Kyprolis, Bendamustine - Treanda, Melphalan - Alkeran

Cohort 3: Carfilzomib 27mgm2

Cohort 1: Carfilzomib 15 mg/m2 DRUG

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

Also known as: Carfilzomib - Kyprolis, Bendamustine - Treanda, Melphalan - Alkeran

Cohort 1: Carfilzomib 15 mg/m2

Cohort 2: Carfilzomib 20 mg/m2 DRUG

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

Also known as: Carfilzomib - Kyprolis, Bendamustine - Treanda, Melphalan - Alkeran

Cohort 2: Carfilzomib 20 mg/m2

Cohort 2b: Carfilzomib 20 mg/m2 DRUG

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

Also known as: Carfilzomib - Kyprolis, Bendamustine - Treanda, Melphalan - Alkeran

Cohort 2b: Carfilzomib 20 mg/m2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Corewell Health West: lead

Study Sites (1)

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Esther Peariso
• Organization: Corewell Health

esther.peariso@corewellhealth.org

616-486-0358

Study Officials

• Muneer H Abidi, MD

  Corewell Health West

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2014
• First Posted: May 28, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: July 26, 2024
• Results First Posted: July 26, 2024

Record last verified: 2024-02

Locations

US (1)