DS Stage I Plasma Cell MyelomaPhase 1/2NCT01842308
Carfilzomib and Melphalan Before Stem Cell Transplant in Treating Patients With Multiple Myeloma
A Phase 1/2 study testing Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carfilzomib in people with DS Stage I Plasma Cell Myeloma and DS Stage II Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma
- What is being tested?
- Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carfilzomib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Jun 2013to 28 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 24Show fewer
- 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
Who cannot join
- 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:
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Phase 1/2 Trial of Carfilzomib and Melphalan and Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma (CARAMEL)
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:
- 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:
- 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:
- 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
- Being tested
- Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation, Carfilzomib, Laboratory Biomarker Analysis, Melphalan
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Bone Marrow TransplantationProcedure or surgery
Also called ABMT, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation
Undergo autologous stem cell transplant
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplantation
Undergo autologous stem cell transplant
CarfilzomibDrug
Also called Kyprolis, PR-171
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | 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. Receives: Procedure: Autologous Bone Marrow Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carfilzomib; Other: Laboratory Biomarker Analysis; Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to day 30
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.
Measured: Up to 5 years
Secondary outcomes (3)
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.
Measured: Up to 5 years
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.
Measured: At day 100
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
Measured: At 1 year and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2013 (estimated)
- Study start4 Jun 2013
- Primary completion11 Oct 2017
- Study completion28 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DS Stage I Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Suzanne Hayman, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01842308
- Sponsor's protocol ID
- MC1185
- Other IDs
- NCI-2013-00550, MC1185, P30CA015083
- Status last verified
- Oct 2019
- First submitted
- 25 Apr 2013
- Last updated
- 1 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of Carfilzomib and Melphalan and Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma (CARAMEL)
- ClinicalTrials.gov ID
- NCT01842308
- Acronym / sponsor ID
- MC1185
- Conditions
- DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Jun 2013 (actual)
- Primary completion
- 11 Oct 2017 (actual)
- Study completion
- 28 Oct 2019 (actual)
- First posted
- 29 Apr 2013 (estimated)
- Results
- Posted 1 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Procedure: Autologous Bone Marrow Transplantation, Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Carfilzomib, Other: Laboratory Biomarker Analysis, Drug: MelphalanCONDITIONING: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Serum creatinine =< 2 mg/dL
- Absolute neutrophil count >= 1000/uL
- Platelet count >= 50,000/uL
- Hemoglobin >= 8.0 g/dL
- Diagnosis of symptomatic MM
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Bone Marrow TransplantationAlso: ABMT, Autologous Bone Marrow Transplant, Autologous Marrow TransplantationUndergo autologous stem cell transplant | Procedure or surgery | Treatment |
| Autologous Hematopoietic Stem Cell TransplantationAlso: Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell TransplantationUndergo autologous stem cell transplant | Procedure or surgery | Treatment |
| CarfilzomibAlso: Kyprolis, PR-171Given IV | Drug | Treatment |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment |
| MelphalanAlso: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustardGiven IV | Drug | Treatment |
Primary outcome
Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level
Time frame: Up to day 30
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.
Percentage of Patients With 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 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.
3 secondary outcomes
Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Up to 5 years
Complete Response Rate at Day 100
Time frame: At day 100
Progression Free Percentage at 1 and 2 Years Post Registration
Time frame: At 1 year and 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for DS Stage I Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
Active, not recruitingPhase 3
Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
RecruitingPhase 3
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma
DS Stage I Multiple Myeloma, DS Stage II Multiple Myeloma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne Hayman principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous Bone Marrow Transplantation, Autologous Hematopoietic Stem Cell Transplantation and Carfilzomib in people with DS Stage I Plasma Cell Myeloma and DS Stage II Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level (time frame: Up to day 30). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2020.