Hodgkin's DiseasePhase 1/2NCT00667615

Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)

A Phase 1/2 study testing rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim in people with Hodgkin's Disease and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 60 years and older
Conditions the study is for: Hodgkin's Disease, Lymphoma
What is being tested?: rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 5 sitesUnited States
Study dates: Apr 2008to Feb 2017
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 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

MSKCC or Weill Cornell biopsy confirmation of relapsed/refractory diffuse large B-cell lymphoma.Patients with large cell transformation of a low-grade B-cell lymphoma will be eligible.
One or two prior chemotherapy regimens not including autologous stem cell transplantation.
Age ≥ 60 years.
Not a candidate for autologous stem cell transplantation.
Patient must have performance status of ≤2 on the ECOG Performance Scale.
Measurable disease

Show all 9Show fewer

Adequate organ and bone marrow function: ANC ≥ 1000/mm3, platelet count ≥ 50,000/mm3, total bilirubin ≤ 1.5 ULN (with exception of Gilbert's disease), AST/ALT ≤ 2.5 ULN, creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 ml/min, potassium and magnesium within normal limits.
Male patients agree to use an adequate method of contraception for the duration of the study.
Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.

Who cannot join

Patient who has had chemotherapy, radiotherapy, or biological therapy [including growth factors], within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) or who has not recovered from adverse events due to agents administered more than 30 days earlier. Patients on a stable dose of steroids for at least 4 weeks prior to onset of study therapy may be included.
Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s).
Patient had prior treatment with an HDAC inhibitor (e.g., romidespin (Depsipeptide),NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103,CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
Patients with active CNS lymphoma and/or lymphomatous meningitis are excluded. However, patients with a history of CNS lymphoma and/or lymphomatous meningitis who have been stable without evidence of CNS and/or leptomeningeal recurrence would be eligible. They must be off steroids or on a stable dose of steroids.
Patient with a primary central nervous system lymphoma.
Patient has known hypersensitivity to the components of study drug or its analogs.

Show all 15Show fewer

Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
Patient is expecting to father children within the projected duration of the study.
Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.
Patient is HIV +.
Patient has active hepatitis B or C.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Memorial Sloan Kettering Cancer Center @ BaskingRidge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical Center
New York, New York
Memorial Sloan Kettering Cancer Center @ Phelps
Sleepy Hollow, New York, 10591

Other trials in United States

About this study

Official title: A Multi-Center Phase I/II Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)

The purpose of this study is to replace a drug with many side effects, procarbazine, with a new novel drug, vorinostat, in a drug combination for the treatment of patients with diffuse large B-cell lymphoma. Vorinostat is the first of a new type of chemotherapy drug, known as a histone deacetylase inhibitor, to be approved by the Food and Drug Administration. It is approved for the treatment of certain lymphomas of the skin. It alters the cancer cell pathway by preventing cancer cells from reproducing. Vorinostat will be added to a combination of four other effective chemotherapy drugs that have been used for many years for the treatment of diffuse large B-cell lymphoma: rituximab, cyclophosphamide, etoposide and prednisone. The doses of vorinostat will be increased or decreased depending on the side effects that occur in each of the first few patients in the trial to find the safest dose with the least side effects. This is termed the phase I part of the clinical trial. Once the best dose of vorinostat is found, the rest of the patients in the clinical trial will be treated with this dose. This is termed the phase II part of the trial. The object of the trial is to find out what effects, good and/or bad, the combination of vorinostat, rituximab, cyclophosphamide, etoposide and prednisone will have on you and your lymphoma.

Conditions: Hodgkin's Disease, Lymphoma
Being tested: rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim
Keywords: vorinostat, rituximab, cyclophosphamide, etoposide, prednisone, Quality of life, 08-045
Medical subject headings: Hodgkin Disease, Lymphoma

What participants receive

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

rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastimDrug
Patients will be treated with 6 cycles of rituximab, cyclophosphamide, etoposide, prednisone and vorinostat every 4 weeks. Quality of life determinations will be obtained at the beginning of each cycle of chemotherapy and at each visit during the first year of followup.

Study groups in NCT00667615
Study group	Role	What they receive
1	Experimental	vorinostat in combination with cyclophosphamide, etoposide,prednisone and rituximab,peg-filgrastim or filgrastim Receives: Drug: rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastim

What is being measured

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

Maximum Tolerated Dose (MTD) of Vorinostat Given Orally for 10 Days in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma
Maximum Tolerated Dose (MTD) of Vorinostat reflects the highest dose of Ridaforolimus and Vorinostat that did not cause a new Grade 2 toxicity in >= 50% of participants
Measured: through study completion, an average of 1 year

Secondary outcomes (1)

Complete Response Rate to Rituximab and a Combination of Vorinostat With Cyclophosphamide, Etoposide, and Prednisone in Elderly Pts With Relapsed Diffuse Large B-cell Lymphoma Who Aren't Candidates for Autologous Stem Cell Transplantation.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.
Measured: through study completion, an average of 1 year

Timeline

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

Apr 2008Feb 2017

First posted28 Apr 2008 (estimated)
Study startApr 2008
Primary completionFeb 2017
Study completionFeb 2017

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.
Other trials for Hodgkin's DiseaseStudies of the same condition, open and under way.
More trials run by Memorial Sloan Kettering Cancer CenterThe 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00667615
Sponsor's protocol ID: 08-045
Status last verified: Feb 2017
First submitted: 24 Apr 2008
Last updated: 5 Jan 2018
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

All Hodgkin's Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Center Phase I/II Trial of Vorinostat in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)
ClinicalTrials.gov ID: NCT00667615
Acronym / sponsor ID: 08-045
Conditions: Hodgkin's Disease, Lymphoma
Keywords: vorinostat, rituximab, cyclophosphamide, etoposide, prednisone, Quality of life, 08-045
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC, Northwestern University, Endeavor Health, Weill Medical College of Cornell University
Study start: Apr 2008 (actual)
Primary completion: Feb 2017 (actual)
Study completion: Feb 2017 (actual)
First posted: 28 Apr 2008 (estimated)
Results: Posted 7 Nov 2017

Clinical summary

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

Study design

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

Arm	Type	Receives
1	Experimental	Drug: rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastimvorinostat in combination with cyclophosphamide, etoposide,prednisone and rituximab,peg-filgrastim or filgrastim

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

MSKCC or Weill Cornell biopsy confirmation of relapsed/refractory diffuse large B-cell lymphoma.Patients with large cell transformation of a low-grade B-cell lymphoma will be eligible.
One or two prior chemotherapy regimens not including autologous stem cell transplantation.
Age ≥ 60 years.
Not a candidate for autologous stem cell transplantation.
Patient must have performance status of ≤2 on the ECOG Performance Scale.

Key exclusion criteria (15 listed)

Patient who has had chemotherapy, radiotherapy, or biological therapy [including growth factors], within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) or who has not recovered from adverse events due to agents administered more than 30 days earlier. Patients on a stable dose of steroids for at least 4 weeks prior to onset of study therapy may be included.
Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s).
Patient had prior treatment with an HDAC inhibitor (e.g., romidespin (Depsipeptide),NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103,CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
Patients with active CNS lymphoma and/or lymphomatous meningitis are excluded. However, patients with a history of CNS lymphoma and/or lymphomatous meningitis who have been stable without evidence of CNS and/or leptomeningeal recurrence would be eligible. They must be off steroids or on a stable dose of steroids.
Patient with a primary central nervous system lymphoma.

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
rituximab, cyclophosphamide, etoposide, prednisone, vorinostat and QOL questionnaire, peg-filgrastim or filgrastimPatients will be treated with 6 cycles of rituximab, cyclophosphamide, etoposide, prednisone and vorinostat every 4 weeks. Quality of life determinations will be obtained at the beginning of each cycle of chemotherapy and at each visit during the first year of followup.	Drug	1

Primary outcome

Maximum Tolerated Dose (MTD) of Vorinostat Given Orally for 10 Days in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma
Time frame: through study completion, an average of 1 year
Maximum Tolerated Dose (MTD) of Vorinostat reflects the highest dose of Ridaforolimus and Vorinostat that did not cause a new Grade 2 toxicity in >= 50% of participants

1 secondary outcome

Complete Response Rate to Rituximab and a Combination of Vorinostat With Cyclophosphamide, Etoposide, and Prednisone in Elderly Pts With Relapsed Diffuse Large B-cell Lymphoma Who Aren't Candidates for Autologous Stem Cell Transplantation.
Time frame: through study completion, an average of 1 year

Results and safety

Results posted to the registry on 7 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Relapsed or Refractory Diffuse Large B-cell Lymphoma	30	30

Primary outcome: Maximum Tolerated Dose (MTD) of Vorinostat Given Orally for 10 Days in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma

Time frame: through study completion, an average of 1 year. Number. Unit: mg/m2

Measure	Relapsed or Refractory Diffuse Large B-cell Lymphoma n = 30
Value	300

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 5 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Relapsed or Refractory Diffuse Large B-cell Lymphoma	19 of 30 (63.3%)	30 of 30 (100%)	25 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.

Related trials for Hodgkin's Disease

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

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.

David Straus, MD principal investigator

Memorial Sloan Kettering Cancer Center

5 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 9 inclusion and 15 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 5 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 7 Nov 2017). 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?

Maximum Tolerated Dose (MTD) of Vorinostat Given Orally for 10 Days in Combination With Cyclophosphamide, Etoposide, Prednisone and Rituximab for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma (time frame: through study completion, an average of 1 year). 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 NCT00667615.

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 5 Jan 2018.