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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01842308
First received: April 25, 2013
Last updated: April 28, 2014
Last verified: April 2014
  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. 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
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: carfilzomib
Drug: melphalan
Procedure: autologous bone marrow transplantation
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 (MTD), defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (Phase I) [ Time Frame: Up to day 30 ] [ Designated as safety issue: Yes ]
  • Proportion of complete responses, defined as a CR noted as the objective status on two consecutive evaluations (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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:
  • Complete response rate [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Adverse event rate, graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 68
Study Start Date: June 2013
Estimated Primary Completion Date: May 2015 (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.

Drug: carfilzomib
Given IV
Other Names:
  • Kyprolis
  • PR-171
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: autologous bone marrow transplantation
Undergo autologous stem cell transplant
Other Names:
  • ABMT
  • bone marrow transplantation, autologous
  • transplantation, autologous bone marrow
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous stem cell transplant
Other: laboratory biomarker analysis
Correlative studies

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:

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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Serum creatinine =< 2 mg/dL
  • Absolute neutrophil count >= 1000/μL
  • Platelet count >= 50,000/μL
  • 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/m2)
  • 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, or Mayo Clinic Florida for treatment and follow-up

    • 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 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 - Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Suzanne Hayman Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01842308     History of Changes
Other Study ID Numbers: MC1185, NCI-2013-00550
Study First Received: April 25, 2013
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

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
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014