Adult Lymphocyte Depletion Hodgkin LymphomaPhase 1/2NCT01535924

Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

A Phase 1/2 study testing gemcitabine hydrochloride and bendamustine hydrochloride in people with Adult Lymphocyte Depletion Hodgkin Lymphoma and Adult Lymphocyte Predominant Hodgkin Lymphoma, run by Beth Christian at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma
What is being tested?: gemcitabine hydrochloride and bendamustine hydrochloride
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 2 sitesUnited States
Study dates: 9 Feb 2012to 20 Feb 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Histologically documented Classical Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy; core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable
Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes:
Nodular sclerosis Hodgkin's lymphoma
Lymphocyte-rich Hodgkin's lymphoma
Mixed cellularity Hodgkin's lymphoma
Lymphocyte depletion Hodgkin's lymphoma

Show all 26Show fewer

Nodular lymphocyte predominant Hodgkin's lymphoma
Patients must have relapsed or progressed after at least one prior therapy
Patients with relapsed or refractory disease following stem cell transplantation are permitted
No prior treatment with bendamustine; prior therapy with gemcitabine is permitted
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable
Measurable disease: lesions that can be accurately measured in at least two dimensions as >= 1.0 x 1.0 cm by computerized tomography (CT), PET/CT (positron emission tomography/CT), or magnetic resonance imaging (MRI)
Non-measurable disease: all other lesions, including small lesions (less than 1.0 x 1.0 cm) and truly non-measurable lesions; lesions that are considered non-measurable include the following:
Bone lesions (lesions if present should be noted)
Ascites
Pleural/pericardial effusion
Lymphangitis cutis/pulmonis
Bone marrow (involvement by Hodgkin's lymphoma should be noted)
Non-pregnant and non-nursing; due to the teratogenic potential of these agents, pregnant or nursing patients may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
Patients with human immunodeficiency virus (HIV) infection are eligible; patients with HIV infection must meet the following: No evidence of co-infection with hepatitis B or C; cluster of differentiation (CD)4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL; no history of acquired immune deficiency syndrome (AIDS) defining conditions
Granulocytes >= 1000/μl
Platelet count >= 75,000/μl
Creatinine =< 20 mg/dL
Bilirubin =< 2.0 mg/dL
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limits of normal

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Emory University
Atlanta, Georgia, 30322
Ohio State University Medical Center
Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I/II Study Of Gemcitabine And Bendamustine In Patients With Relapsed Or Refractory Hodgkin's Lymphoma

This phase I/II trial studies the side effects and best dose of bendamustine hydrochloride when given together with gemcitabine hydrochloride and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in patients with relapsed or refractory Hodgkin's lymphoma.

II. To determine the overall response rate of bendamustine and gemcitabine in patients with relapsed and refractory Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

To determine whether therapy with bendamustine in the setting of relapsed or refractory Hodgkin's lymphoma will impact future stem cell collection.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study.

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 2 years, then every 6 months for up to 3 years.

Conditions: Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Recurrent Adult Hodgkin Lymphoma
Being tested: gemcitabine hydrochloride, bendamustine hydrochloride
Keywords: Hodgkin's Lymphoma, relapsed, refractory
Medical subject headings: Hodgkin Disease, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

gemcitabine hydrochlorideDrug
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
bendamustine hydrochlorideDrug
Also called bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
Given IV

Study groups in NCT01535924
Study group	Role	What they receive
Treatment (combination chemotherapy)	Experimental	Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: gemcitabine hydrochloride; Drug: bendamustine hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I)
Dose limiting toxicity will be defined during cycle 1 only of the phase I trial. Hematologic and Infectious Dose Limiting Toxicities include: Grade 3 febrile neutropenia persisting> 7 days, Grade 4 infection or febrile neutropenia. Treatment delay>14 days due to grade 3-4 neutropenia or thrombocytopenia. Non-Hematological Dose Limiting Toxicities include: any Grade 3 or 4 non-hematologic toxicity related to study treatment with the exception of nausea or vomiting, alopecia, or electrolyte/glucose abnormalities that are correctable within 72 hours.
Measured: up to 5 years

Secondary outcomes (1)

Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II)
Tested using Simon's two-stage Minimax design. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate.
Measured: up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Feb 201220 Feb 2019

First posted20 Feb 2012 (estimated)
Study start9 Feb 2012
Primary completion20 Feb 2019
Study completion20 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Adult Lymphocyte Depletion Hodgkin LymphomaStudies of the same condition, open and under way.
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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01535924
Sponsor's protocol ID: OSU-11015
Other IDs: NCI-2012-00022
Status last verified: Oct 2021
First submitted: 6 Feb 2012
Last updated: 19 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Cohen JB, Wei L, Maddocks KJ, Christian B, Heffner LT, Langston AA, Lechowicz MJ, Porcu P, Flowers CR, Devine SM, Blum KA. Gemcitabine and bendamustine is a safe and effective salvage regimen for patients with recurrent/refractory Hodgkin lymphoma: Results of a phase 1/2 study. Cancer. 2020 Mar 15;126(6):1235-1242. doi: 10.1002/cncr.32640. Epub 2019 Dec 10.
PubMed 31821549

Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study Of Gemcitabine And Bendamustine In Patients With Relapsed Or Refractory Hodgkin's Lymphoma
ClinicalTrials.gov ID: NCT01535924
Acronym / sponsor ID: OSU-11015
Conditions: Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Recurrent Adult Hodgkin Lymphoma
Keywords: Hodgkin's Lymphoma, relapsed, refractory
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Beth ChristianUniversity, hospital or other
Study start: 9 Feb 2012 (actual)
Primary completion: 20 Feb 2019 (actual)
Study completion: 20 Feb 2019 (actual)
First posted: 20 Feb 2012 (estimated)
Results: Posted 19 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in patients with relapsed or refractory Hodgkin's lymphoma.

II. To determine the overall response rate of bendamustine and gemcitabine in patients with relapsed and refractory Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

To determine whether therapy with bendamustine in the setting of relapsed or refractory Hodgkin's lymphoma will impact future stem cell collection.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study.

After completion of study treatment, patients are followed up every 3-6 months for 2 years, then every 6 months for up to 3 years.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (combination chemotherapy)	Experimental	Drug: gemcitabine hydrochloride, Drug: bendamustine hydrochloridePatients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses 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 (26 listed)

Histologically documented Classical Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy; core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable
Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes:
Patients must have relapsed or progressed after at least one prior therapy
Patients with relapsed or refractory disease following stem cell transplantation are permitted
No prior treatment with bendamustine; prior therapy with gemcitabine is permitted

Key exclusion criteria (0 listed)

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
gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV	Drug	Treatment (combination chemotherapy)
bendamustine hydrochlorideAlso: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, TreandaGiven IV	Drug	Treatment (combination chemotherapy)

Primary outcome

Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I)
Time frame: up to 5 years
Dose limiting toxicity will be defined during cycle 1 only of the phase I trial. Hematologic and Infectious Dose Limiting Toxicities include: Grade 3 febrile neutropenia persisting> 7 days, Grade 4 infection or febrile neutropenia. Treatment delay>14 days due to grade 3-4 neutropenia or thrombocytopenia. Non-Hematological Dose Limiting Toxicities include: any Grade 3 or 4 non-hematologic toxicity related to study treatment with the exception of nausea or vomiting, alopecia, or electrolyte/glucose abnormalities that are correctable within 72 hours.

1 secondary outcome

Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II)
Time frame: up to 5 years

Results and safety

Results posted to the registry on 19 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1 (Dose Level 1)	3	3
Phase 1 (Dose Level 2)	3	3
Phase 1 (Dose Level 3)	3	3
Phase 1 (Dose Level 4)	4	4
Phase 2 (Dose Level 5)	6	6
Phase 2	7	7

Primary outcome: Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I)

Time frame: up to 5 years. Number. Unit: number of patients

Measure	Phase 1 (Dose Levels 1) n = 3	Phase 1 (Dose Levels 2) n = 3	Phase 1 (Dose Levels 3) n = 3	Phase 1 (Dose Levels 4) n = 4	Phase 2 (Dose Levels 5) n = 0	Phase 2 n = 0
Value	0	0	0	0	–	–

Population analysed: Only patients in Phase I analyzed

1 secondary outcome is reported in the full results.

Adverse events

Time frame: The Adverse event information was collected for study patients from baseline through study completion utilizing the CTCAE version 4.0 to determine the severity of the reaction for adverse event reporting from baseline to after study completion, up to 5 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1 (Dose Levels 1)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1 (Dose Levels 2)	3 of 3 (100%)	3 of 3 (100%)	0 of 3
Phase 1 (Dose Levels 3)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1 (Dose Levels 4)	4 of 4 (100%)	4 of 4 (100%)	0 of 4
Phase 2 (Dose Levels 5)	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Phase 2	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 31821549Cohen JB, Wei L, Maddocks KJ, Christian B, Heffner LT, Langston AA, Lechowicz MJ, Porcu P, Flowers CR, Devine SM, Blum KA. Gemcitabine and bendamustine is a safe and effective salvage regimen for patients with recurrent/refractory Hodgkin lymphoma: Results of a phase 1/2 study. Cancer. 2020 Mar 15;126(6):1235-1242. doi: 10.1002/cncr.32640. Epub 2019 Dec 10.
JameslineLink provided by the sponsor.

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.

Beth Christian, MD principal investigator

Ohio State University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 26 inclusion and 0 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 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) (time frame: up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01535924, which also lists 1 linked publication.

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 19 Nov 2021.