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Waldenstrom's MacroglobulinemiaPhase 1NCT00150462

Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

A Phase 1 study testing Carfilzomib and Dexamethasone in people with Waldenstrom's Macroglobulinemia and Non-Hodgkin's Lymphoma, run by Amgen at 5 sites in United States.

Completed

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

Official record
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Trial summary

The purpose of this study is to test the safety and tolerability of carfilzomib at different dose levels on hematological cancers such as multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's disease, or Waldenstrom's macroglobulinemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carfilzomib and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
5 sitesUnited States
Study dates
Sep 2005to Oct 2009
Phase
Phase 1
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

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Males and females ≥18 years of age
  • Histologically confirmed diagnosis of one of the hematologic malignancies below:
  • Multiple myeloma (MM)
  • Non-Hodgkin's lymphoma (NHL)
  • Waldenström's Macroglobulinemia (WM)
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  • Hodgkin's disease (HD)
  • Subjects who are refractory or relapsed following at least two prior therapies
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
  • Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of < 3.0 times the upper limit of normal
  • Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥ 1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³
  • Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
  • Subjects receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation
  • An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault
  • Serum creatinine ≤ 2.0 mg/dL
  • Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
  • Female subjects of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test. Male subjects must use an effective barrier method of contraception throughout the study and for three months following the last dose if sexually active with a female of child-bearing potential.

Who cannot join

  • Female subjects who are pregnant or lactating
  • Subjects who are transfusion dependent
  • Subjects with NHL or HL who have received steroid therapy in the previous seven days
  • Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
  • Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
  • For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
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  • Subjects who have received allogeneic stem cell transplant therapy
  • Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
  • Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
  • Major surgery within three weeks before Day 1
  • Congestive heart failure (CHF) (New York Heart Association class III to IV)
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  • Subjects who are known or suspected of having human immunodeficiency virus (HIV) infection or who are HIV seropositive
  • Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid (RNA) or hepatitis B antigen
  • Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer with stable prostate specific antigen (PSA) levels for three years
  • Subjects with treatment-related myelodysplastic disorder
  • Subjects with known brain metastasis (active central nervous system [CNS] disease only)
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Participation in an investigational therapeutic study within one month prior to Day 1
  • Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
  • Concurrent therapy with approved or investigative anticancer therapeutics
  • Subjects with previous hypersensitivity to bortezomib injection
  • Subjects with contraindications to receiving allopurinol
  • Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
  • Subjects with known or suspected amyloidosis
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211-1850

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

  • Weil Medical College of Cornell University

    New York, New York, 10021

  • Herbert Irving Comprehensive Cancer Center, Columbia University

    New York, New York, 10032

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies

The purpose of this study is to test the safety and tolerability of carfilzomib at different dose levels on hematological cancers such as multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's disease, or Waldenstrom's macroglobulinemia. Carfilzomib is a proteasome inhibitor, an enzyme responsible for degrading a wide variety of cellular proteins.

Keywords
Hematological, Proteasome, Myeloma, Lymphoma
Medical subject headings
Waldenstrom Macroglobulinemia, Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma, Neoplasms, Plasma Cell, Lymphoma

What participants receive

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

  • CarfilzomibDrug

    Also called PR-171, Kyprolis

    Administered as an IV bolus dose

  • DexamethasoneDrug

    Administered orally prior to carfilzomib

Study groups in NCT00150462
Study groupRoleWhat they receive
CFZ 1.2 mg/m²ExperimentalParticipants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 2.4 mg/m²ExperimentalParticipants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 4.0 mg/m²ExperimentalParticipants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 6.0 mg/m²ExperimentalParticipants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 8.4 mg/m²ExperimentalParticipants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 11.0 mg/m²ExperimentalParticipants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 15.0 mg/m²ExperimentalParticipants received carfilzomib 115.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 20.0 mg/m²ExperimentalParticipants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 27.0 mg/m²ExperimentalParticipants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 20/27 mg/m²ExperimentalParticipants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Receives: Drug: Carfilzomib
CFZ 20/27 mg/m² + DEXExperimentalParticipants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Receives: Drug: Carfilzomib; Drug: Dexamethasone

What is being measured

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

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    A DLT was defined as any of the following occurring in the first 28 days of study participation:

    Nonhematologic:

    • > Grade 2 neuropathy with pain
    • ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, or diarrhea)
    • ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy

    Hematologic:

    • Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10ˆ9/L) lasting ≥ 14 days without hematopoietic growth factor support
    • Febrile neutropenia (ANC < 1.0 × 10ˆ9/L with a fever ≥ 38.3°C)
    • Grade 4 thrombocytopenia (platelets < 25.0 × 10ˆ9/L) or thrombocytopenia associated with bleeding.

    Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0.

    Measured: 28 days

  2. Maximum Observed Plasma Concentration of Carfilzomib (Cmax)

    Measured: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

  3. Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)

    Measured: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

  4. Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib

    Measured: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

  5. Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib

    Measured: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

Secondary outcomes (4)
  1. Best Clinical Response to Treatment

    Disease response criteria for NHL were according to the International Working Group Criteria for Non-Hodgkin's Lymphoma. Disease response criteria for Multiple Myeloma were according to the European Group for Blood and Marrow Transplantation (EBMT). Disease response criteria for WM were according to the consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. The disease response criteria for Hodgkin's Lymphoma are defined as follows:

    • Complete response: total resolution of measurable disease parameters.
    • Partial response: a ≥ 50% resolution without the appearance of new disease.
    • Stable disease: between < 50% resolution and ≤ 25% increases in measurable disease parameters without appearance of new disease.
    • Progressive disease: an increase of > 25% in measurable disease parameters.

    Best clinical response is the best response observed from the start of study treatment until disease progression or death.

    Measured: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

  2. Duration of Response

    Duration of objective response is defined as the time from the date of first documented assessment of clinical response (confirmed or unconfirmed complete response, partial response, or minimal response) to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment.

    Median duration of response was calculated using the Kaplan-Meier method.

    Measured: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

  3. Time to Progression

    Time to progressive disease is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease, plus one day. Participants without tumor progression were censored at the date of their last clinical response assessment.

    Median time to progression was calculated using the Kaplan-Meier method.

    Measured: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

  4. Progression-free Survival

    Progression-free survival is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment. Median progression-free survival was calculated using the Kaplan-Meier method.

    Measured: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

Timeline

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

  1. First posted8 Sep 2005 (estimated)
  2. Study startSep 2005
  3. Primary completionOct 2009
  4. Study completionOct 2009

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00150462
Sponsor's protocol ID
PX-171-002
Status last verified
Apr 2017
First submitted
6 Sep 2005
Last updated
2 May 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib and Dexamethasone in people with Waldenstrom's Macroglobulinemia and Non-Hodgkin's Lymphoma, run by Amgen at 5 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 18 inclusion and 26 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 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 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.

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 3 Dec 2015). 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?

Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: 28 days). 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?
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 2 May 2017.

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