Carfilzomib and Melphalan Before Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT ID: NCT01842308

Last Updated: 2020-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-04
• Study Completion Date: 2019-10-28

Brief Summary

This phase I/II trial studies the side effects and best dose of carfilzomib when given together with melphalan and to see how well they work in treating patients with multiple myeloma before stem cell transplant. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with melphalan may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of carfilzomib that can be added to high dose melphalan as part of conditioning chemotherapy for myeloma. (Phase I) II. To determine the efficacy of the combination in patients with myeloma undergoing stem cell transplantation, as defined by achievement of complete response (CR). (Phase II)

SECONDARY OBJECTIVES:

I. To examine the toxicities associated with addition of carfilzomib to high dose melphalan in patients with multiple myeloma (MM).

II. To determine the progression free rate at 1 and 2 years post registration.

TERTIARY OBJECTIVES:

I. To determine the proportion of patients achieving a minimal residual disease (MRD) negative status.

II. To assess the HevyLite assay prior to and during treatment.

OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study.

CONDITIONING: Patients receive carfilzomib intravenously (IV) over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3.

TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.

After completion of study treatment, patients are followed up at day 30, day 100, and then every 90 days for up to 5 years.

Conditions

DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Study Design

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

Study Groups

Treatment

CONDITIONING: Patients receive carfilzomib IV over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3.

TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.

Group Type: EXPERIMENTAL

Autologous Bone Marrow Transplantation

Intervention Type: PROCEDURE

Undergo autologous stem cell transplant

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo autologous stem cell transplant

Carfilzomib

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Melphalan

Intervention Type: DRUG

Given IV

Interventions

Autologous Bone Marrow Transplantation

Undergo autologous stem cell transplant

Intervention Type: PROCEDURE

Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous stem cell transplant

Intervention Type: PROCEDURE

Carfilzomib

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Melphalan

Given IV

Intervention Type: DRUG

Other Intervention Names

ABMT; Autologous Bone Marrow Transplant; Autologous Marrow Transplantation; Autologous Hematopoietic Cell Transplantation; Autologous Stem Cell Transplantation; Kyprolis; PR-171; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine mustard; L-Sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine Nitrogen Mustard; Sarcoclorin; Sarkolysin; WR-19813

Eligibility Criteria

Inclusion Criteria

• Serum creatinine =< 2 mg/dL
• Absolute neutrophil count >= 1000/uL
• Platelet count >= 50,000/uL
• Hemoglobin >= 8.0 g/dL
• Diagnosis of symptomatic MM
• Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:

• Serum monoclonal protein >= 1.0 g/dL
• >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain >=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Bone marrow plasma cells >= 30%
• NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis
• NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy
• Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m^2)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)
• Provide informed written consent
• Ejection fraction >= 45%
• Corrected pulmonary diffusion capacity of greater than or equal to 50%
• Forced expiratory volume in 1 second (FEV1) >= 50%
• Forced vital capacity (FVC) >= 50%
• Negative pregnancy test performed =< 7 days prior to registration, for women of childbearing potential only
• Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida for treatment

• Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
• Willing to provide blood and bone marrow samples for correlative research purposes

Exclusion Criteria

• Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant
• More than two prior regimens for therapy of MM
• 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; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV)
• Other active malignancy < 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
• Any of the following:

• Pregnant women or women of reproductive capability who are unwilling to use effective contraception
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
• Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
• Concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suzanne Hayman

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-00550

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC1185

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC1185

Identifier Type: -

Identifier Source: org_study_id