Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer

January 2, 2019 updated by: University of California, Davis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • University of California Davis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus + Bendamustine
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.
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • Treanda
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
Drug: everolimus
Given PO
Other Names:
  • Afinitor
  • RAD001
  • 42-O-(2-hydroxy)ethyl rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
Time Frame: Up to 30 days post-treatment
Up to 30 days post-treatment
Response rates (complete response, partial response, stable disease)
Time Frame: Up to 30 days post-treatment
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Up to 30 days post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Collaborators

Novartis

Investigators

  • Principal Investigator: Mehrdad Abedi, University of California, Davis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

April 9, 2018

Study Completion (Actual)

April 9, 2018

Study Registration Dates

First Submitted

September 12, 2014

First Submitted That Met QC Criteria

September 15, 2014

First Posted (Estimate)

September 16, 2014

Study Record Updates

Last Update Posted (Actual)

January 4, 2019

Last Update Submitted That Met QC Criteria

January 2, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 637004 (Registry Identifier: UC Davis)
  • CRAD001NUS235T
  • UCDCC#245 (Other Identifier: University of California, Davis)
  • NCI-2014-01934 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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