AzTrials
AzTrials

Contiguous Stage II Adult Diffuse Large Cell LymphomaPhase 1/2NCT02073097

Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

A Phase 1/2 study testing Carfilzomib, Rituximab and Cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by Case Comprehensive Cancer Center 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
Search all trials

Trial summary

This phase I/II trial studies the side effects and best dose of carfilzomib when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with diffuse large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carfilzomib, Rituximab and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
3 sitesUnited States
Study dates
28 Jan 2015to 29 Jun 2023
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

  • Patients must have histologically confirmed diffuse large B-cell lymphoma (DLBCL); patients with previously diagnosed indolent lymphoma (follicular lymphoma and marginal zone lymphoma but not small lymphocytic lymphoma) who have transformed to DLBCL are eligible only if they have not previously been treated for indolent lymphoma. For the Phase II study, patients must have non-GC DLBCL as determined by Hans Algorithm.
  • Patients must have radiographically measurable disease
  • Patients may have received brief (<15 days) treatment with glucocorticoids and/or 1 cycle of chemotherapy such as R-CHOP [or some component(s) thereof] for the diagnosis of B-cell lymphoma provided they had all necessary staging tests performed prior to R-CHOP including CT and/or PET/CT scans, echocardiogram and bone marrow biopsy. Treatment must occur within 60 days prior to enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; performance status of 3 will be accepted if impairment is caused by DLBCL complications and improvement is expected once therapy is initiated
  • Hemoglobin ≥ 7.0 g/dl
  • Absolute neutrophil count ≥ 1,500/mcL
Show all 20Show fewer
  • Platelet count ≥ 100,000/mcL
  • Total bilirubin within normal institutional limits unless due to Gilbert's disease
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X institutional upper limit of normal
  • Creatinine clearance ≥ 45 mL/min calculated by Cockcroft-Gault
  • Adequate cardiac function left ventricular ejection fraction (LVEF) > 50% as assessed by echocardiogram or MUGA (Multi Gated Acquisition Scan)
  • The effects of Carfilzomib on the developing human fetus are unknown. For this reason and because chemotherapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 2 weeks prior to initiation of treatment, for the duration of study participation and for 3 months after completing treatment. Should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately. Men must agree to refrain from sperm donation for at least 90 days after the last dose of carfilzomib.
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • International Prognostic Index must be documented:
  • ECOG performance status ≥ 2 (1 point)
  • Age ≥ 60 (1 point)
  • ≥ 2 extranodal sites (1 point)
  • Lactate dehydrogenase (LDH) > upper limit of normal (1 point)
  • Ann Arbor stage III or IV (1 point)

Who cannot join

  • Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Known CNS involvement by lymphoma. Patients at high risk for secondary CNS involvement but without neurologic symptoms suspected to be due to lymphoma are allowed to be enrolled and receive intrathecal chemotherapy including but not limited to methotrexate, cytarabine and glucocorticoids. Patients who are enrolled and subsequently identified to have pathologic confirmation of CNS involvement by lymphoma may be continued on study at the discretion of the principal investigator.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or other agents (R-CHOP) used in this study
  • Active congestive heart failure (New York heart Association Class III or IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within four months prior to enrollment
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
Show all 11Show fewer
  • Pregnant or breastfeeding women are excluded from this study because Carfilzomib is a proteasome inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with Carfilzomib, breastfeeding should be discontinued if the mother is treated with Carfilzomib. These potential risks may also apply to other agents used in this study.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Carfilzomib. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or low-risk prostate cancer after curative therapy, or low risk melanoma if treated with definitive therapy (such as excision) and expected to have a low likelihood of recurrence.
  • Patients who have had major surgical procedures or significant traumatic injury within 28 days prior to study treatment
  • Patients who are reported to be of direct Asian-Pacific (China, Japan, Taiwan, Singapore, Republic of Korea, and Thailand) ancestry.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

  • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: A Phase I/II Study of Carfilzomib in Combination With R-CHOP (CR-CHOP) for Patients With Diffuse Large B-cell Lymphoma

This phase I/II trial studies the side effects and best dose of carfilzomib when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with diffuse large B-cell lymphoma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth by finding cancer cells and helping kill them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not known if carfilzomib in combination with R-CHOP is better or worse than R-CHOP alone in treating patients with diffuse large b-cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of carfilzomib in combination with rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) (CR-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and identify a recommended phase II dose (RP2D). (Phase I)

SECONDARY OBJECTIVES:

  1. To determine if CR-CHOP improves the rates of 1-year progression free survival (PFS) and overall survival (OS) in non-germinal center (non-GC) DLBCL patients relative to historical controls treated with R-CHOP(Phase II) II. To determine response rates (complete and partial remission) in non-GC DLBCL patients treated with CR-CHOP and compare to historical controls treated with R-CHOP.

III. Because a proportion (~10%) of patients classified as non-GC by immunohistochemical (IHC) algorithms may not have the activated B-cells (ABC) subtyped of DLBCL, an exploratory secondary objective will compare the PFS, OS and response rates of the ABC subgroup of patients with DLBCL as determined by the Gene Expression Profiling with those of the overall group of non-GC DLBCL.

OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study.

Patients receive rituximab intravenously (IV) over at least 90 minutes, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 3-5 minutes, vincristine sulfate IV over 1 minute on day 1, and prednisone orally (PO) on days 1-5. Patients also receive carfilzomib IV over 30 minutes on days 1, 2, 8 and 9. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and at 6, 12, and 24 months.

Medical subject headings
Lymphoma, Large B-Cell, Diffuse

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, according to dose level. Cohorts begin with dose level (DL)1, escalated in standard 3+3 design to identify a recommended phase 2 dose DL (-2) 11 mg/m2 on day 1 and 2 every 21 days, cycles 1-6

    DL (-1) 15 mg/m2 on days 1 and 2 every 21 days, cycles 1-6

    DL (1) 20 mg/m2 days 1,2 every 21 days, cycles 1-6

    DL (2) 20 mg/m2 days 1,2 of cycle 1 followed by 27 mg/m2 days 1,2 every 21 days for cycles 2-6.

    DL (3) 20 mg/m2 days 1,2 of cycle 1 followed by 36 mg/m2 days 1,2 every 21 days for cycles 2-6.

    DL(4) 20 mg/m2 days 1,2 of cycle 1 followed by 45 mg/m2 days 1,2 every 21 days for cycles 2-6

    DL (5) 20 mg/m2 days 1,2 of cycle 1 followed by 56 mg/m2 days 1,2 every 21 days for cycles 2-6

  • RituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV (375mg/m^2)

  • CyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV (750mg/m^2)

  • Doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV (50mg/m^2)

  • Vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV (1.4mg/m^2)

  • PrednisoneDrug

    Also called DeCortin, Deltra

    Given PO (100mg)

  • PegfilgrastimDrug

    Also called Neulasta, Recombinant methionyl human granulocyte colony-stimulating factor (G-CSF)

    6 mg SC day 4 (every 21 days). Filgrastim 300 or 480 mcg IV/SC daily days 1-10 may be substituted if pegfilgrastim is not available. ONPROTM is also an acceptable method of administration.

  • AcyclovirDrug

    Also called Zovirax

    PO (400mg)

Study groups in NCT02073097
Study groupRoleWhat they receive
rituximab, combination chemotherapy, carfilzomibExperimentalParticipants receive (every 21 day cycle): * Rituximab IV over at least 90 minutes on day 2 * Carfilzomib IV over 30 minutes on days 1, and 2 * Cyclophosphamide IV over 30-60 minutes on day 3 * Doxorubicin hydrochloride IV over 3-5 minutes on day 3 * Vincristine sulfate IV over 1 minute on day 3 * Prednisone PO on days 3-7 any time * Pegfilgrastim day 4 * Acyclovir 2x per day from cycle 1, 6 months after completion of cycle 6 Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carfilzomib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin hydrochloride; Drug: Vincristine sulfate; Drug: Prednisone; Drug: Pegfilgrastim; Drug: Acyclovir

What is being measured

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

  1. Recommended Phase II Dose (Phase I)

    Highest dose administered when no more than 1 out of 6 patients experience lose limiting toxicity below the maximally administered dose.

    Measured: Through cycle 6 (each cycle is 21 days)

Secondary outcomes (4)

  1. Progression Free Survival (Phase II)

    PFS will be estimated using a Kaplan-Meier curve. Progression-free Survival (PFS) is defined as the time from entry onto study until lymphoma progression or death from any cause. Participants was evaluated utilizing RECIST v1.0 criteria at baseline, 3 months after beginning treatment, end of treatment (6 cycles of therapy), and at 6 month, 12 month, and 24 month follow up visit. RECIST v1.0 criteria for Malignant Lymphoma use the following categories of response: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Relapse and Progression (PD).

    Measured: 31 months after treatment

  2. Overall Survival (Phase II)

    Overall survival will be estimated with a Kaplan-Meier curve. Overall survival is defined as the time from entry onto study until lymphoma progression or death from any cause.

    Measured: 31 months after treatment

  3. Complete Response Rate (Phase II)

    The percentage of patients with a complete response as defined by a complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy

    Measured: 31 months after treatment

  4. Partial Response Rate (Phase II)

    The percentage of patients with a partial response as defined a >50% decrease in the sum of the product of the diameter of up to six of the largest nodes; no increase in the any node, liver, or spleen; no new sites of disease.

    Measured: 31 months after treatment

Timeline

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

  1. First posted27 Feb 2014 (estimated)
  2. Study start28 Jan 2015
  3. Primary completion20 Jul 2021
  4. Study completion29 Jun 2023

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02073097
Sponsor's protocol ID
CASE3413
Status last verified
May 2024
First submitted
25 Feb 2014
Last updated
29 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carfilzomib, Rituximab and Cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by Case Comprehensive Cancer Center 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 20 inclusion and 11 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 29 May 2024. 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 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 29 May 2024). 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?

Recommended Phase II Dose (Phase I) (time frame: Through cycle 6 (each cycle is 21 days)). 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 NCT02073097.

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 29 May 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in