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

  • STATUS
    Recruiting
  • End date
    Sep 29, 2021
  • participants needed
    50
  • sponsor
    Case Comprehensive Cancer Center
Updated on 29 March 2021
ct scan
platelet count
cancer
cyclophosphamide
chronic lymphocytic leukemia
rituximab
absolute neutrophil count
vincristine
ejection fraction
monoclonal antibodies
prednisone
measurable disease
gilbert's syndrome
doxorubicin
combination chemotherapy
follicular lymphoma
diffuse large b-cell lymphoma
b-cell lymphoma
antineoplastic

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. 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.

Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

Details
Condition Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma
Treatment Rituximab, cyclophosphamide, laboratory biomarker analysis, acyclovir, doxorubicin hydrochloride, prednisone, vincristine sulfate, pegfilgrastim, Carfilzomib
Clinical Study IdentifierNCT02073097
SponsorCase Comprehensive Cancer Center
Last Modified on29 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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)
extranodal sites (1 point)
Lactate dehydrogenase (LDH) > upper limit of normal (1 point)
Ann Arbor stage III or IV (1 point)

Exclusion Criteria

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
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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note