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

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Mayo Clinic
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01842308
First received: April 25, 2013
Last updated: July 10, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma Refractory Plasma Cell Myeloma Procedure: Autologous Bone Marrow Transplantation Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carfilzomib Other: Laboratory Biomarker Analysis Drug: Melphalan Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Trial of Carfilzomib and Melphalan and Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma (CARAMEL)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Maximum tolerated dose (Phase I) [ Time Frame: Up to day 30 ]
    Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients.

  • Proportion of complete responses, defined as a complete response noted as the objective status on two consecutive evaluations (Phase II) [ Time Frame: Up to 5 years ]
    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.


Secondary Outcome Measures:
  • Adverse event rate, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

  • Complete response rate [ Time Frame: At day 100 ]
    Estimated by the total number of patients who achieve a complete response by day 100 post-transplant divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate at day 100 will be calculated.

  • Time to progression [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed at 1 year ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Time to progression [ Time Frame: Time from registration to the earliest date with documentation of disease progression, assessed at 2 years ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.


Estimated Enrollment: 68
Actual Study Start Date: June 4, 2013
Estimated Study Completion Date: May 30, 2018
Estimated Primary Completion Date: May 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Procedure: Autologous Bone Marrow Transplantation
Undergo autologous stem cell transplant
Other Names:
  • ABMT
  • Autologous Bone Marrow Transplant
  • Autologous Marrow Transplantation
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • Autologous Stem Cell Transplantation
Drug: Carfilzomib
Given IV
Other Names:
  • Kyprolis
  • PR-171
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Melphalan
Given IV
Other Names:
  • 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01842308

Locations
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Vivek Roy         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Suzanne R. Hayman         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Suzanne Hayman Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01842308     History of Changes
Other Study ID Numbers: MC1185
NCI-2013-00550 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1185 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Study First Received: April 25, 2013
Last Updated: July 10, 2017

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Mechlorethamine
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2017