Bendamustine Hydrochloride in Treating Patients With Recurrent or Progressive Anaplastic Glioma

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00823797
• Collaborator: National Cancer Institute (NCI) (NIH), National Comprehensive Cancer Network (Other)
• Enrollment: 45
• Locations: 3
• Arm: 1
• Duration (Months): 102
• Patients Per Site: 15
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well bendamustine hydrochloride works in treating patients with anaplastic glioma or glioblastoma that has come back (recurrent) or growing, spreading or getting worse (progressive). Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm	Drug: Bendamustine Hydrochloride; Other: Quality-of-Life Assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. The primary endpoint for this study is the 6-month progression-free survival-i.e., the proportion of patients who remain alive and free of any tumor progression at 6 months.

SECONDARY OBJECTIVES:

1. To determine the safety of single agent bendamustine (Treanda) (bendamustine hydrochloride) the treatment of malignant gliomas.

2. To determine the efficacy of bendamustine (Treanda) as a single agent as assessed by progression-free survival (PFS) at 6 months.

3. To assess quality of life using the Functional Assessment of Cancer Therapy-Brain (FACT-BR).

OUTLINE:

Patients receive bendamustine hydrochloride intravenously (IV) over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bendamustine in the Treatment of Recurrent High-Grade Gliomas (Anaplastic Gliomas and Glioblastoma)
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (bendamustine hydrochloride) Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Bendamustine Hydrochloride; Given IV; Other Names: Bendamustin Hydrochloride Cytostasan Hydrochloride Levact Ribomustin SyB L-0501 Treanda ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. PFS-6 [At 6 months]

   Defined as the proportion of patients who remain alive and free of any disease progression at 6 months. PFS over time will be estimated using the Kaplan-Meier method with standard errors estimated using Greenwood's formula.

Secondary Outcome Measures

1. PFS [Up to progression or death, whichever came first, assessed up to 108 months]

   Defined as the time from date of initial therapy to first objective documentation of tumor progression or death.

2. Toxic Death [Up to 30 days after completion of study treatment]

   Defined as death that is possibly, probably, or definitely attributed to bendamustine hydrochloride.

3. Overall Survival [Until death or last reported survival]

   *inclusive of subjects still alive at time of last reporting.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have had prior pathologic confirmation of tumor histology, anaplastic glioma (AG) or glioblastoma (GBM) and have supratentorial gliomas

• Patients must have shown unequivocal evidence for tumor recurrence or progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan with contrast

• The recurrence to be treated needs to be the 1st or 2nd recurrence of the AG or GBM

• If a patient has had surgery prior to enrolling on study, an enhanced MRI or CT scan should be done within 96 hours prior to surgery or at least 4-6 weeks after surgery

• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

• They are > 2 weeks from surgery

• They have recovered from the effects of surgery

• Evaluable or measurable disease following resection of recurrent tumor is mandated for eligibility into the study

• To best assess the extent of residual disease post-operatively, an enhanced CT/MRI should be done no later than 96 hours after surgery or it will need to be done 4-6 weeks post-operatively; if the 96 hour scan is more than 2 weeks from registration, the scan needs to be repeated

• A baseline scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for at least 5 days otherwise a new baseline MR/CT is required; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement

• Patients must have failed prior external beam radiation therapy; a positron emission tomography (PET) or thallium single photon emission computed tomography (SPECT), MR spectroscopy and MR perfusion, or surgical documentation may be done at the discretion of the treating physician if there is a question of radiation changes/necrosis versus progressive disease

• Stereotactic radiosurgery (SRS):

• Patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease

• At least 12 weeks between completion of SRS and initiation of bendamustine

• Interstitial brachytherapy: patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease

• Patients must have had at least one prior chemotherapy regimen that included temozolomide and no more than one prior salvage chemotherapy

• Patients must have recovered from the toxic effects of prior therapy: 4 weeks from prior cytotoxic therapy and/or at least 2 weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count), 4 weeks for experimental biologic agents (epidermal growth factor receptor [EGFR] inhibitors, etc) and 7 weeks from Gliadel implantation

• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information

• Patients must have a life expectancy > 11 weeks

• Patients must have a Karnofsky performance status of > 60

• White blood cells (WBC) >= 3,000/ul

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 80,000/mm^3

• Hemoglobin >= 9 mg/dl (NOTE: eligibility level for hemoglobin may be reached by transfusion)

• Absolute lymphocyte count >= 200/mm^3

• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) < 3 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Serum creatinine < 1.5 mg/dL

• Calculated creatinine, glomerular filtration rate (GFR) >= 30 cc/minute

Exclusion Criteria:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

• Known human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study

• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible

• Patients must not be pregnant or breast feeding and must practice adequate contraception

• Patients can only be on non-enzyme inducing anti-convulsants; if they are on an enzyme inducing anti-convulsant, they may be converted to a non-enzyme inducing anticonvulsants

• Patients cannot be taking any cytochrome P450, cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) pathway inhibiting or inducing agents (except proton pump inhibitors which are allowed) including cimetidine, antidepressants, antibiotics and all others

• Known sensitivity to bendamustine

• Known sensitivity to mannitol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
3	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)
• National Comprehensive Cancer Network

Investigators

• Principal Investigator: Maciej Mrugala, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maciej Mrugala, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00823797
• Other Study ID Numbers: 6803; NCI-2010-00714; 6803; P30CA015704
• First Posted: Jan 16, 2009
• Last Update Posted: Jul 7, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Glioblastoma; Astrocytoma; Gliosarcoma; Oligodendroglioma; Brain Neoplasms; Recurrence; Bendamustine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma	Treatment (Bendamustine Hydrochloride) for Glioblastoma
Arm/Group Description	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	29	16
COMPLETED	29	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma	Treatment (Bendamustine Hydrochloride) for Glioblastoma	Total
Arm/Group Description	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	29	16	45
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 96.6%	13 81.3%	41 91.1%
>=65 years	1 3.4%	3 18.8%	4 8.9%
Sex: Female, Male (Count of Participants)
Female	12 41.4%	6 37.5%	18 40%
Male	17 58.6%	10 62.5%	27 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.4%	0 0%	1 2.2%
Not Hispanic or Latino	28 96.6%	16 100%	44 97.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.4%	0 0%	1 2.2%
Asian	1 3.4%	1 6.3%	2 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.4%	0 0%	1 2.2%
White	26 89.7%	14 87.5%	40 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 6.3%	1 2.2%
Region of Enrollment (Count of Participants)
United States	29 100%	16 100%	45 100%

Outcome Measures

1. Primary Outcome

Title	PFS-6
Description	Defined as the proportion of patients who remain alive and free of any disease progression at 6 months. PFS over time will be estimated using the Kaplan-Meier method with standard errors estimated using Greenwood's formula.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Glioblastoma	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma
Arm/Group Description	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	16	29
Count of Participants [Participants]	1 3.4%	8 50%

2. Secondary Outcome

Title	PFS
Description	Defined as the time from date of initial therapy to first objective documentation of tumor progression or death.
Time Frame	Up to progression or death, whichever came first, assessed up to 108 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Glioblastoma	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma
Arm/Group Description	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	16	29
Median (95% Confidence Interval) [months]	1.0	2.6

3. Secondary Outcome

Title	Toxic Death
Description	Defined as death that is possibly, probably, or definitely attributed to bendamustine hydrochloride.
Time Frame	Up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Glioblastoma	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma
Arm/Group Description	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	16	29
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Overall Survival
Description	*inclusive of subjects still alive at time of last reporting.
Time Frame	Until death or last reported survival

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Bendamustine Hydrochloride) for Glioblastoma	Treatment (Bendamustine Hydrochloride) for Anaplastic Glioma
Arm/Group Description	Glioblastoma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.	Anaplastic Glioma Arm Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	16	29
Median (95% Confidence Interval) [months]	18.3	45.6

Adverse Events

Arm/Group Title	Treatment (Bendamustine Hydrochloride)
Arm/Group Description	Patients receive bendamustine hydrochloride IV over 30-90 minutes on days 1-2. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Bendamustine Hydrochloride: Given IV Quality-of-Life Assessment: Ancillary studies
All Cause Mortality
	Treatment (Bendamustine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Bendamustine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	3/45 (6.7%)
Immune system disorders
Allergic Reaction	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/45 (4.4%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Bendamustine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
Blood and lymphatic system disorders
Lymphopenia	36/45 (80%)
Thrombocytopenia	9/45 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.