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

Primary Purpose

Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
everolimus
bendamustine hydrochloride
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Adult Diffuse Large Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California Davis

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus + Bendamustine

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
Response rates (complete response, partial response, stable disease)
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.

Full Information

First Posted
September 12, 2014
Last Updated
January 2, 2019
Sponsor
University of California, Davis
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02240719
Brief Title
Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer
Official Title
Phase I Study of Everolimus + Bendamustine in Patients With Relapsed/Refractory Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
April 9, 2018 (Actual)
Study Completion Date
April 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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). 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, Refractory Chronic Lymphocytic Leukemia, Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus + Bendamustine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
bendamustine hydrochloride
Other Intervention Name(s)
bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Incidence and severity of adverse events as defined by the NCI CTCAE version 4.03
Time Frame
Up to 30 days post-treatment
Title
Response rates (complete response, partial response, stable disease)
Description
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Time Frame
Up to 30 days post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mehrdad Abedi
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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