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Multiple MyelomaPhase 1/2NCT01246063

Carfilzomib, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1/2 study testing carfilzomib, pegylated liposomal doxorubicin (PLD) and Dexamethasone in people with Multiple Myeloma, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The aim of this phase I/II trial is to determine the maximal tolerated dose (MTD) of carfilzomib together with pegylated liposomal doxorubicin hydrochloride (PLD) with or without dexamethasone, and then to establish the efficacy and safety of this novel combination in patients with relapsed or refractory multiple… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
carfilzomib, pegylated liposomal doxorubicin (PLD) and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
14 May 2012to 23 Mar 2018
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

  • Histologically confirmed diagnosis of multiple myeloma with a measurable disease parameter at time of screening; a measurable disease parameter is defined as one or more of the following:
  • Serum monoclonal protein >= 0.5 g/dl
  • 24 hour urine monoclonal protein >= 0.2 g/24 hour
  • Serum free light chain ratio > 5 x normal ratio with an absolute difference of 10mg/dl between the involved and uninvolved free light chain
  • Soft tissue plasmacytoma >= 2 cm measurable by either physical examination and/or applicable radiographs (e.g. magnetic resonance imaging [MRI], computed tomography [CT], etc)
  • Bone Marrow Plasma Cells >= 30%
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  • Documentation of at least one line of prior myeloma therapy now with relapsed or refractory disease requiring re-treatment
  • At least 18 years of age at the time of signing the informed consent.
  • Performance status of Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 60%; participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
  • Required laboratory values
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 x the upper limit of the institutional normal value (ULN)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Absolute neutrophil count (ANC) >= 1,000
  • Hemoglobin >= 8 g/dl
  • Platelets >= 50,000
  • Creatinine clearance > 15 ml/minute using Cockcroft-Gault formula
  • For those participants receiving warfarin (Coumadin), unfractionated heparin, or low-molecular weight heparin therapy, the applicable coagulation parameter that is being monitored must be within the accepted therapeutic ranges for those indications
  • Transfusions and/or growth factor dependent participants are not excluded if the above parameters can be achieved with such support
  • Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence during that time frame; FCBP must agree to regular pregnancy testing during this timeframe; inclusion of FCBP requires two negative pregnancy tests prior to enrollment. All women, regardless of age, should be considered FCBP unless they are surgically sterile (post hysterectomy, post bilateral oophorectomy, etc) or have been naturally post menopausal for >= 24 consecutive months
  • Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug
  • Ability to understand and willing to sign a written informed consent document

Who cannot join

  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma Cell Leukemia
  • Waldenstrom's macroglobulinemia
  • Pregnant or lactating females
  • Use of any anti-myeloma drug therapy within 14 days of initiation of study drug treatment excluding corticosteroids if given for an indication other than myeloma; bisphosphonates are not considered anti-myeloma drugs
  • Participation in an investigational therapeutic study within 14 days of initiation of study drug treatment
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  • Radiotherapy to multiple sites or immunotherapy within 14 days of initiation of study drug treatment (localized radiotherapy to a single site at least 7 days before start is permissible)
  • Major surgery within 14 days of initiation of study drug treatment
  • Participants in whom the required program of oral (PO) and IV fluid hydration is contraindicated
  • Prior history of a hypersensitivity reaction to PLD, doxorubicin, bortezomib, carfilzomib, or liposomal drug formulations other than PLD; history of reactions to liposomal drug formulations other than PLD should be evaluated individually and if their reactions were felt to have been due to the encapsulated agent, rather than the liposomal component itself they should be excluded at the discretion of the investigators
  • Participants who are known to have active hepatitis A, B, or C viral infection may not participate in this study; active disease is defined as participants with a known viral hepatitis whose liver function tests are elevated
  • Known human immunodeficiency virus (HIV)-seropositive and are taking anti-retrovirals may not participate in this study; participants who are HIV-seropositive and not on anti-retroviral therapy and who otherwise meet the inclusion/exclusion criteria will be eligible for the study
  • Compromised cardiovascular function defined as any of the following:
  • Electrocardiogram (EKG) evidence of acute ischemia
  • EKG evidence of medically significant conduction system abnormalities
  • History of myocardial infarction within the last 6 months
  • Unstable angina pectoris or cardiac arrhythmia
  • History of Class 3 or Class 4 New York Heart Association Congestive Heart Failure within 6 months of enrollment on study
  • Left ventricular ejection fraction (LVEF) < 45% by either echocardiography or radionuclide-based multiple gated acquisition (Echo or MUGA)
  • Uncontrolled concurrent illness including: other hematologic or non-hematologic malignancy, active infection, or uncontrolled diabetes
  • Any significant psychological, medical, or surgical condition thought to compromise the participant, the study, or prevent informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma

The aim of this phase I/II trial is to determine the maximal tolerated dose (MTD) of carfilzomib together with pegylated liposomal doxorubicin hydrochloride (PLD) with or without dexamethasone, and then to establish the efficacy and safety of this novel combination in patients with relapsed or refractory multiple myeloma

Being tested
carfilzomib, pegylated liposomal doxorubicin (PLD), Dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • carfilzomibDrug

    Also called Kyprolis, CFZ

  • pegylated liposomal doxorubicin (PLD)Drug

    Also called DOXIL

  • DexamethasoneDrug

    Also called Decadron

Study groups in NCT01246063
Study groupRoleWhat they receive
Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)ExperimentalDose Level 0: Carfilzomib IV (20 mg/m^2) D1\&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD)
Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)ExperimentalDose Level 1: Carfilzomib IV (20 mg/m^2) D1\&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (1 dose level above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (1 dose level above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (1 dose level above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Dose Level 2: Carfilzomib IV (2 dose levels above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (2 dose levels above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (2 dose levels above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD)
Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)ExperimentalDose Level 2: Carfilzomib IV (20 mg/m^2) D1\&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD)
Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)ExperimentalDose Level 3: Carfilzomib IV (20 mg/m^2) D1\&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD)
Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)ExperimentalCohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD); Drug: Dexamethasone
Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)ExperimentalCarfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Receives: Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD); Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1).

    • MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.
    • Please note that the maximum tolerated dose of carfilzomib and pegylated liposomal doxorubicin was not reached. The data below is the recommended dosage for further studies.

    Measured: 28 days (completion of first cycle of all Phase I - Part 1 patients)

  2. Maximum Tolerated Dose (MTD) of Carfilzomib and PLD (Phase I - Part 2).

    -MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.

    Measured: 28 days (completion of first cycle of all Phase I - Part 2 patients)

  3. Maximum Tolerated Dose (MTD) of Dexamethasone (Phase I - Part 2).

    -MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.

    Measured: 28 days (completion of first cycle of all Phase I - Part 2 patients)

  4. Phase 2 - Efficacy of Carfilzomib in Combination With PLD and Dexamethasone as Measured by the Percentage of Participants With Confirmed Tumor Responses

    -A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria.

    Measured: Completion of treatment (median number of cycles was 9.5 (range 1-34))

  5. Phase 2 - Toxicity of Carfilzomib in Combination With PLD and Dexamethasone as Measured by Number of Participants Who Experience Grade 3/4 Toxicity

    Measured: Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))

Secondary outcomes (3)

  1. Median Overall Survival

    Measured: Completion of follow-up (median of 23.3 months)

  2. Progression-free Survival Time (Phase 2 Only)

    -Progression per IMWG Criteria

    Measured: Through completion of follow-up (median follow-up was 23.3 months)

  3. Median Duration of Overall Response

    • For participants with confirmed tumor responses
    • A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria

    Measured: Through completion of follow-up (median follow-up was 23.3 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2010 (estimated)
  2. Study start14 May 2012
  3. Primary completion28 Dec 2017
  4. Study completion23 Mar 2018

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01246063
Sponsor's protocol ID
201102043
Status last verified
Apr 2019
First submitted
15 Nov 2010
Last updated
8 Apr 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schroeder MA, Fiala MA, Huselton E, Cardone MH, Jaeger S, Jean SR, Shea K, Ghobadi A, Wildes T, Stockerl-Goldstein KE, Vij R. A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma. Clin Cancer Res. 2019 Jul 1;25(13):3776-3783. doi: 10.1158/1078-0432.CCR-18-1909. Epub 2019 Apr 5.

    PubMed 30952640

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing carfilzomib, pegylated liposomal doxorubicin (PLD) and Dexamethasone in people with Multiple Myeloma, run by Washington University School of Medicine at 1 site 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 21 inclusion and 21 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 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 8 Apr 2019). 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?

Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1). (time frame: 28 days (completion of first cycle of all Phase I - Part 1 patients)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01246063, which also lists 1 linked publication.

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 8 Apr 2019.

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