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Lymphoma, Non-HodgkinPhase 1NCT02187133

Carfilzomib With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Phase 1 study testing Carfilzomib, Bendamustine and Rituximab in people with Lymphoma, Non-Hodgkin and Lymphoma, run by University of California, San Francisco at 3 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

This study will be conducted as a Phase Ib, open-label, non-randomized, single-institution study to evaluate the safety and tolerability of carfilzomib in combination with bendamustine and rituximab in patients with relapsed or refractory NHL and to determine the recommended phase II dose and preliminary efficacy of… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin, Lymphoma
What is being tested?
Carfilzomib, Bendamustine and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
5 May 2015to 31 Mar 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 B-cell non-Hodgkin's lymphoma (Mantle Cell Lymphoma, Follicular Lymphoma, Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma, Diffuse Large B-cell Lymphoma, and Lymphoplasmacytic Lymphoma)
  • Must have relapsed or refractory disease after 2 or more prior lines of therapy; 1 line of therapy is allowed, if it included an autologous stem cell transplant and at least 12 weeks have elapsed from Day 0. A line of therapy is defined as a course of therapy that is not interrupted by progressive disease.
  • Subjects must have measurable disease of at least 1.5 cm in diameter
  • Age ≥ 18 years
  • Life expectancy ≥ 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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  • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception. FCBP definition: A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months.
  • Male subjects must agree to practice contraception for at least 90 days after the last dose of carfilzomib, and must agree not to donate sperm for at least 90 days after the last dose of carfilzomib
  • Adequate bone marrow function:
  • Absolute neutrophil count ≥ 1.0 × 10^9/L
  • Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior Cycle 1, Day 1 (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines)
  • Platelet count ≥ 75 × 10^9/L or≥ 50× 10^9/L if there is lymphoma involvement in the bone marrow, independent of platelet transfusion
  • Adequate hepatic function:
  • Serum aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal
  • Serum direct bilirubin ≤ 2 mg/dL (unless history of Gilbert's)
  • Adequate renal function:
  • Creatinine clearance (CrCl) ≥ 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
  • Uric acid If elevated, corrected to within laboratory range prior to dosing

Who cannot join

  • Progressive disease on bendamustine within 6 months of cycle 1, Day 1
  • Prior treatment with carfilzomib for lymphoma
  • Patient has received other investigational drugs within 21 days prior to Cycle 1, Day 1. Exceptions allowed if greater than four half-lives of the experimental agent ).
  • Prior radiation therapy or chemotherapy within 2 weeks prior Cycle 1, Day 1, monoclonal antibody therapy within 4 weeks
  • Prior allogeneic transplant
  • Active, uncontrolled central nervous system (CNS) involvement by lymphoma
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  • Pregnant or lactating females
  • Major surgery within 14 days prior Cycle 1, Day 1
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior Cycle 1, Day 1
  • Known human immunodeficiency virus infection
  • Active hepatitis C infection (HCV), defined as presence of HCV antibody.
  • Unstable angina or myocardial infarction within 6 months prior Cycle 1, Day 1, New York Heart Association (NYHA) Class III or IV heart failure, left ventricular ejection fraction (LVEF) < 40%, uncontrolled angina, history of severe coronary artery disease, history of torsade de pointes, history of symptomatic pulmonary hypertension, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, QTc prolongation >450 msec, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior Cycle 1, Day 1
  • Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior Cycle 1, Day 1
  • Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior Cycle 1, Day 1
  • Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of California, Davis

    Davis, California, 95616

  • University of California, San Diego

    San Diego, California, 92093

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Phase Ib Dose Escalation Trial of Carfilzomib in Combination With Bendamustine and Rituximab In Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

This study will be conducted as a Phase Ib, open-label, non-randomized, single-institution study to evaluate the safety and tolerability of carfilzomib in combination with bendamustine and rituximab in patients with relapsed or refractory NHL and to determine the recommended phase II dose and preliminary efficacy of this combination. The study will have two phases: a dose-escalation phase to determine the maximal tolerated dose of carfilzomib in this combination where participants will be monitored for toxicity, tolerability and response and a dose-expansion phase that will determine the preliminary efficacy in patients with Mantle cell lymphoma or any other disease subtype in which there is a preliminary efficacy signal observed.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of carfilzomib when combined with bendamustine (bendamustine hydrochloride) and rituximab in patients with relapsed or refractory non-Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

  1. To evaluate the preliminary antitumor activity of carfilzomib with bendamustine and rituximab in patients with non-Hodgkin lymphoma (dose escalation) and with specific non-Hodgkin lymphoma (NHL) subtypes (dose expansion).

OUTLINE: This is a dose-escalation study of carfilzomib.

Patients receive carfilzomib intravenously (IV) over 30 minutes twice weekly on days 1, 2, 8, 9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1 (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks for 6 months, every 3 months for 6 months, and then every 6 months thereafter.

Keywords
Relapsed, Refractory
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Recurrence

What participants receive

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

  • CarfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV; Dose Level (DL)

    Twice Weekly:

    DL -1 and DL 1: 15 mg/m^2

    Weekly:

    DL 1.5: 20,27,27 mg/m^2, DL 2: 20,36,36 mg/m^2, DL 3: 20,56,56 mg/m^2 DL 4: 20,70,70 mg/m^2

  • BendamustineDrug

    Also called Bendamustine Hydrochloride, Cytostasan Hydrochloride, Levacet, Ribomustin

    Given IV; Dose Level (DL)

    DL -1: 75 mg/m^2 DL 1,1.5, 2, 3, and 4: 90 mg/m^2

  • RituximabDrug

    Also called C2B8 Monoclonal Antibody, Rituxan, RTXM83

    Given IV; 375 mg/m^2

Study groups in NCT02187133
Study groupRoleWhat they receive
TreatmentExperimentalPatients receive carfilzomib IV over 30 minutes twice weekly on days 1, 2, 8, 9, 15, and 16 or weekly on days 2, 9, and 16; bendamustine hydrochloride IV over 60 minutes on days 1 and 2; and rituximab IV over 30-90 minutes on day 9 (course 1 only) and day 1 (subsequent courses). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carfilzomib; Drug: Bendamustine; Drug: Rituximab

What is being measured

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

  1. Maximally tolerated dose (MTD)

    The MTD will be the dose level immediately preceding the dose level at which >= 2 Dose Limiting Toxicities (DLT) are observed and at which 0/3 or 1/6 participants experiences a DLT.

    Measured: Up to 1 cycle (28 days per cycle)

  2. Number of participants with Dose Limiting Toxicities (DLT)

    The DLT period will correspond to cycle 1 of therapy. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 will be used to assess the severity of adverse events. The causality of each AE will be assessed by the investigator for confirmation of a DLT.

    Measured: Up to 1 cycle (28 days per cycle)

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    The lymphoma response assessment will be determined using the revised International Working Group (IWG) criteria for Complete Response (CR) defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, a post-treatment residual mass of any size is permitted as long as it is Positron Emission Tomography (PET) negative, the spleen and/or liver, if enlarged before therapy on the basis of the physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, etc. or Partial Response (PR) defined as the post-treatment PET should be positive in at least one previously involved site, At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, No new sites of disease should be observed, etc.

    Measured: Up to 2 years

  2. Median Duration of Response

    Defined as the time from documentation of PR or CR until documented lymphoma progression or receipt of anti-lymphoma therapy or death due to lymphoma. Patients are to be censored at the time of last follow-up or death due to another cause.

    Measured: Up to 2 years

  3. Median Progression Free Survival (PFS)

    Defined as the time from day 1 until lymphoma progression, receipt of anti-lymphoma therapy, or death as a result of any cause. Patients will be censored at the time of last follow up.

    Measured: Up to 2 years

  4. Median Time to Next Therapy

    Time to next therapy is measured from day 1 to receipt of anti-lymphoma therapy or death due to lymphoma. Patients are censored at the time of last follow-up or death unrelated to treatment or disease.

    Measured: Up to 2 years

Timeline

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

  1. First posted10 Jul 2014 (estimated)
  2. Study start5 May 2015
  3. Primary completion31 Mar 2021
  4. Study completion31 Mar 2021

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02187133
Sponsor's protocol ID
14251
Other IDs
NCI-2015-00775
Status last verified
Apr 2021
First submitted
8 Jul 2014
Last updated
23 Apr 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kambhampati S, Fakhri B, Ai WZ, Kaplan LD, Tuscano JM, Wieduwilt MJ, Sudhindra A, Cavallone E, Reiner J, Aoun C, Castillo M, Martinelli M, Ta T, Le D, Padilla M, Crawford E, Andreadis CB. Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial. Clin Lymphoma Myeloma Leuk. 2021 Mar;21(3):139-146. doi: 10.1016/j.clml.2020.12.020. Epub 2020 Dec 24.

    PubMed 33478921

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib, Bendamustine and Rituximab in people with Lymphoma, Non-Hodgkin and Lymphoma, run by University of California, San Francisco at 3 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 19 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 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximally tolerated dose (MTD) (time frame: Up to 1 cycle (28 days per cycle)). 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?

On the ClinicalTrials.gov record for NCT02187133, 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 23 Apr 2021.

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