Recurrent Adult Diffuse Large Cell LymphomaPhase 1NCT02240719
Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer
A Phase 1 study testing everolimus and bendamustine hydrochloride in people with Recurrent Adult Diffuse Large Cell Lymphoma and Recurrent Adult Hodgkin Lymphoma, run by University of California, Davis at 1 site in United States.
Trial summary
This phase I trial studies the side effects and the best dose of everolimus when given together with bendamustine hydrochloride in treating patients with cancer of the blood (hematologic cancer) that has returned after a period of improvement (relapsed) or did not get better with a particular treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma
- What is being tested?
- everolimus and bendamustine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to 9 Apr 2018
- 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
- Measurable disease
- Baseline hemoglobin level of > 7.0 g/dl
- Understand and voluntarily sign an informed consent form
- Able to adhere to the study visit schedule and other protocol requirements
- All the patients need to have biopsy proven active disease at the time of clinical trial
- Eastern Cooperative Oncology Group performance status of =< 2 study entry
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- Absolute neutrophil count >= 1,000/mm^3
- Platelet count >= 50,000/mm^3
- Calculated creatinine clearance > 40 ml/min or 24 hour urine
- Total bilirubin =< 2 x upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper limit of normal
- International normalized ratio < 2
Who cannot join
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
- Any severe and/or uncontrolled medical conditions
- Uncontrolled diabetes mellitus
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of everolimus
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- Known hypersensitivity to everolimus or bendamustine
- Known central nervous system (CNS) disease (NHL, diffuse large B cell lymphoma [DLBCL])
- Recent major surgery within 14 days prior to cycle 1, day 1
- Taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
- Received live attenuated vaccines
- Known sero-positive for active or past viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are sero-positive because of hepatitis B virus vaccine are eligible
- History of another primary malignancy
- History of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
- Pregnant or nursing (lactating) women
- Women of childbearing potential
- Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis
Sacramento, California, 95817
About this study
Official title: Phase I Study of Everolimus + Bendamustine in Patients With Relapsed/Refractory Hematological Malignancies
This phase I trial studies the side effects and the best dose of everolimus when given together with bendamustine hydrochloride in treating patients with cancer of the blood (hematologic cancer) that has returned after a period of improvement (relapsed) or did not get better with a particular treatment (refractory). Everolimus may prevent cancer cells from growing by blocking a protein that is needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving everolimus together with bendamustine hydrochloride may be a better treatment for hematologic cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of everolimus when administered in combination with bendamustine (bendamustine hydrochloride) in defined hematologic malignancies.
II. To determine the safety and tolerability of administering everolimus in combination with bendamustine chemotherapy.
SECONDARY OBJECTIVES:
- To determine the efficacy of everolimus when administered in combination with bendamustine in adult patients with relapsed/refractory hematological malignancies.
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and 2 and everolimus orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma
- Being tested
- everolimus, bendamustine hydrochloride
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Hodgkin Disease, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Given PO
bendamustine hydrochlorideDrug
Also called bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Everolimus + Bendamustine | Experimental | Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: everolimus; Drug: bendamustine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of everolimus, defined as the dose that produces dose-limiting toxicity (DLT) in =< 1/6 patients, determined by incidence of DLT graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Measured: 28 days
Secondary outcomes (2)
Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
Measured: Up to 30 days post-treatment
Response rates (complete response, partial response, stable disease)
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Measured: Up to 30 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2014 (estimated)
- Study startOct 2014
- Primary completion9 Apr 2018
- Study completion9 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Adult Diffuse Large Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Mehrdad Abedi, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02240719
- Sponsor's protocol ID
- 637004
- Other IDs
- 637004, CRAD001NUS235T, UCDCC#245, NCI-2014-01934
- Status last verified
- Jan 2019
- First submitted
- 12 Sep 2014
- Last updated
- 4 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Everolimus + Bendamustine in Patients With Relapsed/Refractory Hematological Malignancies
- ClinicalTrials.gov ID
- NCT02240719
- Acronym / sponsor ID
- 637004
- Conditions
- Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Oct 2014
- Primary completion
- 9 Apr 2018 (actual)
- Study completion
- 9 Apr 2018 (actual)
- First posted
- 16 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and the best dose of everolimus when given together with bendamustine hydrochloride in treating patients with cancer of the blood (hematologic cancer) that has returned after a period of improvement (relapsed) or did not get better with a particular treatment (refractory). Everolimus may prevent cancer cells from growing by blocking a protein that is needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving everolimus together with bendamustine hydrochloride may be a better treatment for hematologic cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of everolimus when administered in combination with bendamustine (bendamustine hydrochloride) in defined hematologic malignancies.
II. To determine the safety and tolerability of administering everolimus in combination with bendamustine chemotherapy.
SECONDARY OBJECTIVES:
- To determine the efficacy of everolimus when administered in combination with bendamustine in adult patients with relapsed/refractory hematological malignancies.
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive bendamustine hydrochloride intravenously (IV) over 30 minutes on days 1 and 2 and everolimus orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus + Bendamustine | Experimental | Drug: everolimus, Drug: bendamustine hydrochloridePatients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2 and everolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Measurable disease
- Baseline hemoglobin level of > 7.0 g/dl
- Understand and voluntarily sign an informed consent form
- Able to adhere to the study visit schedule and other protocol requirements
- All the patients need to have biopsy proven active disease at the time of clinical trial
Key exclusion criteria (18 listed)
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
- Any severe and/or uncontrolled medical conditions
- Uncontrolled diabetes mellitus
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Given PO | Drug | Everolimus + Bendamustine |
| bendamustine hydrochlorideAlso: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, TreandaGiven IV | Drug | Everolimus + Bendamustine |
Primary outcome
MTD of everolimus, defined as the dose that produces dose-limiting toxicity (DLT) in =< 1/6 patients, determined by incidence of DLT graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 28 days
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
2 secondary outcomes
Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
Time frame: Up to 30 days post-treatment
Response rates (complete response, partial response, stable disease)
Time frame: Up to 30 days post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehrdad Abedi principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing everolimus and bendamustine hydrochloride in people with Recurrent Adult Diffuse Large Cell Lymphoma and Recurrent Adult Hodgkin Lymphoma, run by University of California, Davis 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 12 inclusion and 18 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 4 Jan 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 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?
MTD of everolimus, defined as the dose that produces dose-limiting toxicity (DLT) in =< 1/6 patients, determined by incidence of DLT graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). 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 4 Jan 2019.