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CompletedNCT01842308Updated Sep 1, 2020Results posted

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

A Phase 1/2 interventional study of Autologous Bone Marrow Transplantation and Autologous Hematopoietic Stem Cell Transplantation in DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma and DS Stage III Plasma Cell Myeloma, sponsored by Mayo Clinic. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-01.

Sponsored by Mayo Clinic · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
50
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • DS Stage I Plasma Cell Myeloma
  • DS Stage II Plasma Cell Myeloma
  • DS Stage III Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 50 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
50 participants (actual)

Study arms

  • 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 · Procedure: Autologous Hematopoietic Stem Cell Transplantation · Drug: Carfilzomib · Other: Laboratory Biomarker Analysis · Drug: Melphalan

Interventions

  • ProcedureAutologous Bone Marrow Transplantation

    Undergo autologous stem cell transplant

    Also known as: ABMT, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation

  • ProcedureAutologous Hematopoietic Stem Cell Transplantation

    Undergo autologous stem cell transplant

    Also known as: Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation

  • DrugCarfilzomib

    Given IV

    Also known as: Kyprolis, PR-171

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugMelphalan

    Given IV

    Also known as: 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

06

What researchers measure

Primary outcomes

  1. Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level

    Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity(DLT) in at least one-third of patients. For this study, a DLT is any of the following during the first 2 cycles of treatment; Absolute neutrophil count engraftment\* delayed beyond day 21 or Platelet engraftment\* delayed beyond day 30, grade 3+ related sensory or motor neuropathy, or grade 4+ related non-neurologic or non-hematologic adverse event(excluding nausea, vomiting, and diarrhea. Reported below are the number of patients who experienced a DLT.

    Time frame: Up to day 30

  2. Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)

    The percentage 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 percentages will be calculated.

    Time frame: Up to 5 years

Secondary outcomes

  1. Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    These results are reported in the adverse events section. 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.

    Time frame: Up to 5 years

  2. Complete Response Rate at Day 100

    Complete response rate (CRR) is defined as the percentage of complete responses 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 frame: At day 100

  3. Progression Free Percentage at 1 and 2 Years Post Registration

    Progression is an Increase of 25% from lowest value in any of the following (A "25% increase" refers to M protein, FLC and bone marrow results and does not refer to bone lesions, soft tissue plasmacytoma or hypercalcemia. The lowest value does not need to be a confirmed value. If the lowest serum Mprotein is ≥ 5 g/dL, an increase in serum M-protein of ≥ 1 g/dL is sufficient to define disease progression.), (In the case where a value is felt to be a spurious result per physician discretion (for example, a possible lab error), that value will not be considered when determining the lowest value.): Serum M-protein (absolute increase must be ≥ 0.5 g/dL) and/or Urine M-protein (absolute increase must be ≥ 200 mg/24 hrs) and/or If the only measurable disease is FLC, the difference between involved and uninvolved FLC levels (absolute increase must be\>10 mg/dL) and/or If the only measurable disease is BM, bone marrow PC percentage (absolute increase must be ≥ 10%) (Bone marrow criteria for PD

    Time frame: At 1 year and 2 years

07

Results

Posted Sep 1, 2020

Participant flow

Participant flow — Overall Study
MilestonePhase 1: Dose Level 3Phase 1: Dose Level 2Phase 1: Dose Level 1Phase 1: Dose Level 0Phase 2: Dose Level 3
Started633236
Completed633235
Not completed00001
Withdrew: Withdrawal by subject00001

Outcome measures

PrimaryDetermine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level

Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity(DLT) in at least one-third of patients. For this study, a DLT is any of the following during the first 2 cycles of treatment; Absolute neutrophil count engraftment\* delayed beyond day 21 or Platelet engraftment\* delayed beyond day 30, grade 3+ related sensory or motor neuropathy, or grade 4+ related non-neurologic or non-hematologic adverse event(excluding nausea, vomiting, and diarrhea. Reported below are the number of patients who experienced a DLT.

Time frame:
Up to day 30
Reported as:
Count of participants · Participants
Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level
ParticipantsPhase 1: Dose Level 3Phase 1: Dose Level 2Phase 1: Dose Level 1Phase 1: Dose Level 0
Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level1000
PrimaryPercentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)

The percentage 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 percentages will be calculated.

Time frame:
Up to 5 years
Reported as:
Number · percentage of patients
Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)
percentage of patientsDose Level 3
Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)21.95 (10.56 to 37.61)
SecondaryAdverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

These results are reported in the adverse events section. 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.

Time frame:
Up to 5 years
Reported as:
Count of participants · Participants
Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
ParticipantsPhase 1: Dose Level 3Phase 1: Dose Level 2Phase 1: Dose Level 1Phase 1: Dose Level 0Phase 2: Dose Level 3
Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0633235
SecondaryComplete Response Rate at Day 100

Complete response rate (CRR) is defined as the percentage of complete responses 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 frame:
At day 100
Reported as:
Number · percentage of patients
Complete Response Rate at Day 100
percentage of patientsDose Level 3
Complete Response Rate at Day 10017.07 (7.15 to 32.06)
SecondaryProgression Free Percentage at 1 and 2 Years Post Registration

Progression is an Increase of 25% from lowest value in any of the following (A "25% increase" refers to M protein, FLC and bone marrow results and does not refer to bone lesions, soft tissue plasmacytoma or hypercalcemia. The lowest value does not need to be a confirmed value. If the lowest serum Mprotein is ≥ 5 g/dL, an increase in serum M-protein of ≥ 1 g/dL is sufficient to define disease progression.), (In the case where a value is felt to be a spurious result per physician discretion (for example, a possible lab error), that value will not be considered when determining the lowest value.): Serum M-protein (absolute increase must be ≥ 0.5 g/dL) and/or Urine M-protein (absolute increase must be ≥ 200 mg/24 hrs) and/or If the only measurable disease is FLC, the difference between involved and uninvolved FLC levels (absolute increase must be\>10 mg/dL) and/or If the only measurable disease is BM, bone marrow PC percentage (absolute increase must be ≥ 10%) (Bone marrow criteria for PD

Time frame:
At 1 year and 2 years
Reported as:
Number · percentage of patients
Progression Free Percentage at 1 and 2 Years Post Registration
percentage of patientsDose Level 3
1 year90.24 (76.87 to 97.28)
2 years75.61 (59.70 to 87.64)

Adverse events

Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Phase 1; Dose Level 30/6 (0%)3/6 (50%)6/6 (100%)
Phase 1; Dose Level 20/3 (0%)2/3 (66.7%)3/3 (100%)
Phase 1; Dose Level 10/3 (0%)1/3 (33.3%)3/3 (100%)
Phase 1; Dose Level 00/2 (0%)2/2 (100%)2/2 (100%)
Phase 20/35 (0%)16/35 (45.7%)35/35 (100%)
Most frequent serious events
Showing 10 of 33
Most frequent serious events
EventPhase 1; Dose Level 3Phase 1; Dose Level 2Phase 1; Dose Level 1Phase 1; Dose Level 0Phase 2
Atrial fibrillationCardiac disorders0/60/30/31/21/35
Upper respiratory infectionInfections and infestations0/60/30/31/20/35
AnemiaBlood and lymphatic system disorders0/61/30/30/20/35
ColitisGastrointestinal disorders0/61/30/30/21/35
Infections and infestations - Other, specifyInfections and infestations0/61/30/30/20/35
HyperglycemiaMetabolism and nutrition disorders0/60/31/30/20/35
HypophosphatemiaMetabolism and nutrition disorders0/61/30/30/21/35
Sleep apneaRespiratory, thoracic and mediastinal disorders0/60/31/30/20/35
HypertensionVascular disorders1/60/31/30/20/35
HypotensionVascular disorders0/60/31/30/20/35
Most frequent other events
Showing 10 of 46
Most frequent other events
EventPhase 1; Dose Level 3Phase 1; Dose Level 2Phase 1; Dose Level 1Phase 1; Dose Level 0Phase 2
AnemiaBlood and lymphatic system disorders6/62/33/32/231/35
NauseaGastrointestinal disorders1/61/30/32/28/35
CD4 lymphocytes decreasedInvestigations0/60/30/32/20/35
Lymphocyte count decreasedInvestigations4/63/33/32/232/35
Neutrophil count decreasedInvestigations5/63/33/32/230/35
Platelet count decreasedInvestigations6/63/33/32/235/35
White blood cell decreasedInvestigations6/63/33/32/232/35
Peripheral sensory neuropathyNervous system disorders3/62/32/32/219/35
HypotensionVascular disorders3/63/31/30/217/35
Febrile neutropeniaBlood and lymphatic system disorders4/60/31/30/21/35

Baseline characteristics

All patients that began treatment

Age, Continuous
Age, Continuous(years)Phase 1; Dose Level 3Phase 1; Dose Level 2Phase 1; Dose Level 1Phase 1; Dose Level 0Phase 2Total
Median52 (42 to 65)61 (44 to 63)61 (60 to 66)55 (50 to 60)61 (46 to 77)60 (42 to 77)
Sex: Female, Male
Sex: Female, Male(Participants)Phase 1; Dose Level 3Phase 1; Dose Level 2Phase 1; Dose Level 1Phase 1; Dose Level 0Phase 2Total
Female21001417
Male42322132
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Phase 1; Dose Level 3Phase 1; Dose Level 2Phase 1; Dose Level 1Phase 1; Dose Level 0Phase 2Total
Hispanic or Latino000011
Not Hispanic or Latino63223245
Unknown or Not Reported001023
08

Study locations

2 sites
  • Mayo Clinic in Florida
    Jacksonville, Florida 32224-9980, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 27, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 1, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01842308
Lead sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 29, 2013
Start date
Jun 4, 2013
Primary completion
Oct 11, 2017
Completion
Oct 28, 2019
Results posted
Sep 1, 2020
Last update
Sep 1, 2020

Study contacts

Suzanne Hayman
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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