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LymphomaPhase 1NCT02532192

A Phase Ib Study of Belinostat With RDHAP Chemotherapy (Dexamethasone, Cytarabine, Cisplatinum) in Adults With Relapsed or Refractory Diffuse Large B-cell Lymphoma

A Phase 1 study testing Belinostat, Rituximab and Cisplatin in people with Lymphoma, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be combined with standard chemotherapy drugs (rituximab, cisplatin, cytarabine, and dexamethasone) in patients with relapsed or refractory DLBCL who are eligible for an autologous stem cell transplant (a transplant of… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Lymphoma
What is being tested?
Belinostat, Rituximab and Cisplatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2015to Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aggressive B-cell lymphoma, including DLBCL and FL or other indolent or low grade malignancy transforming to DLBCL, Grade III FL, Burkitt lymphoma, and unclassifiable B-cell lymphoma with features of Burkitt and DLBCL according to the World Health Organization, with biopsy confirmation of disease which has relapsed after or refractory to a standard cytotoxic chemotherapy combination including rituximab and doxorubicin, for whom an autologous stem cell transplant is planned.
  • Have received between 1 - 2 prior cytotoxic treatments, not to include belinostat, RDHAP, or autologous or allogeneic stem cell transplant. Radiation which was pre-planned to occur at the conclusion of systemic cytotoxic therapy will not be considered a separate prior therapy. Radiation administered for potential recurrent or relapsed disease will be considered a separate prior therapy.
  • Patient or durable power of attorney (DPA) for healthcare must be able to understand and voluntarily sign an IRB-approved informed consent form.
  • Age 18-80 years at the time of signing the informed consent.
  • Patients must have bi-dimensional measurable disease.
  • Patients with performance status of </=3 (Eastern Cooperative Oncology Group Performance Status Scale, 3 only allowed if decline in status is deemed related to lymphoma and felt potentially reversible by the treating physician).
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  • Within 4 weeks of therapy start, serum bilirubin <1.5x ULN (maximum level based on MD Anderson laboratory ranges is 1.95 mg/dL); AST (SGOT) and ALT (SGPT) </=3x ULN or < 5x ULN if hepatic metastases are present; ANC >1000/mm^3 and platelets >100,000/mm^3 unless deemed likely related to lymphoma involvement in the bone marrow where the minimum ANC allowable will be 500/mm^3 and minimum allowable platelet count will be 50,000/mm^3.
  • Within 4 weeks of therapy start, renal function assessed by calculated creatinine clearance >/= 50ml/min by Cockcroft-Gault formula using actual body weight.
  • Patients must be willing to receive transfusions of blood products.
  • Within 4 weeks of therapy start, women of childbearing potential must have a negative serum (Beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at screening and must adhere to the scheduled pregnancy testing.
  • Women of childbearing potential and men who are sexually active with a woman of childbearing potential must be practicing a highly effective method of birth control during and after the study (12 months for women and 3 months for men), consistent with local regulations regarding the use of birth control methods for subjects participating in this clinical study.

Who cannot join

  • Any serious medical condition including but not limited to uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, COPD, left ventricular ejection fraction of less than 40, active infection, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. Patients with history of cardiac arrhythmias should have cardiac evaluation and clearance.
  • Pregnant or lactating females.
  • Known hypersensitivity to any component of RDHAP.
  • Patients with Gilbert's syndrome unless homozygosity for the UFT1A1*28 mutation has been excluded.
  • HIV infection, active hepatitis B infection, active hepatitis C infection.
  • Known homozygous for UGT1A1*28 mutation from prior testing or family history.
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  • Requirement of therapy with a UGT1A1 Inhibitor, as detailed in Section 8.4, or use within 7 days of enrollment on this protocol.
  • All patients with active central nervous system involvement with lymphoma.
  • Diagnosis of prior malignancy within the past 2 years with the exception of successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast. History of other malignancies are allowed if in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years.
  • Significant neuropathy (Grades 3 - 4, or Grade 2 with pain) within 14 days prior to enrollment.

About this study

The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be combined with standard chemotherapy drugs (rituximab, cisplatin, cytarabine, and dexamethasone) in patients with relapsed or refractory DLBCL who are eligible for an autologous stem cell transplant (a transplant of the patient's own stem cells). The safety of the study drug will also be studied.

Read the detailed description

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to a dose level of belinostat based on when they join this study. Up to 4 dose levels of belinostat will be tested. Between 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of belinostat is found.

All participants will receive the same dose level of the standard chemotherapy drugs.

Study Drug Administration:

Participant will receive belinostat with standard chemotherapy for up to two 21-day cycles.

Participant will receive belinostat by vein on Days 1 and 2 of each cycle. The infusions will last 24 hours.

Participant will receive rituximab and cisplatin by vein on Day 2 of each cycle. Participant will receive cytarabine by vein on Day 2 or 3 of each cycle, depending on when they join this study. Rituximab will be given over 4-5 hours, cisplatin will be given over 3-4 hours, and cytarabine will be given over 1 hour.

Participant will take dexamethasone once a day by mouth on Days 2-5 of both study cycles.

Blood (about 5 tablespoons) and bone marrow will be collected about 10 business days (Monday-Friday) before participant begins receiving belinostat. The blood and bone marrow will be used for peripheral blood mononuclear cell (PBMC) testing. This testing is designed to learn if participant will respond to treatment. To collect a bone marrow biopsy, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Participant will also receive filgrastim, pegfilgrastim, SMX, valacyclovir, ciprofloxacin and fluconazole to reduce side effects. Participant's study doctor will discuss with them when and how they will take these drugs.

If participant's doctor thinks it is necessary, they will also have a bone marrow biopsy and aspirate performed to check the status of the disease within 4 weeks before they begin receiving belinostat. To collect a bone marrow biopsy/aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

Study Visits:

Within 5 working/business days before the start of each cycle:

  • Participant will have a physical exam.
  • Blood (about 4-6 tablespoons) will be drawn for routine tests.

One (1) time a week after the completion of therapy during each cycle, blood (about 4-6 tablespoons) will be drawn for routine tests.

Blood (about 4 tablespoons) will be drawn on Days 1,2, 3, and 21 (+/- 72 hours) of Cycles 1 and 2 for PBMC testing.

Length of Treatment:

Participant may continue taking belinostat combined with chemotherapy for up to 3 cycles. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the follow-up visits.

End-of-Dosing Visit:

Within 3 weeks after the start of the last cycle:

  • Participant will have a physical exam.
  • Blood (about 4-6 tablespoons) will be drawn for routine and PBMC testing.
  • Participant will have an FDG-PET/CT scan to check the status of the disease.
  • If participant's doctor thinks it is necessary, they may have a bone marrow biopsy and aspirate to check the status of the disease
  • If participant's doctor thinks it is necessary, they may have a core needle biopsy to check the status of the disease. To perform a core biopsy, a sample of tissue is removed using a hollow core needle that has a cutting edge.

This is an investigational study. Belinostat is FDA approved to treat T-cell lymphoma. Its use in this study is investigational. The standard chemotherapy drugs are commercially available and FDA approved to treat DLBCL.

Up to 40 participants will be enrolled on this study. All will be enrolled at MD Anderson.

Conditions
Lymphoma
Being tested
Belinostat, Rituximab, Cisplatin, Cytarabine, Dexamethasone
Keywords
Lymphoma, Diffuse large B-cell lymphoma, DLBCL, Relapsed, Refractory, Belinostat, Rituximab, Rituxan, Cisplatin, Platinol-AQ, Platinol, CDDP, Cytarabine, Ara-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride, Dexamethasone, Decadron, Ciprofloxacin
Medical subject headings
Lymphoma, Lymphoma, Large B-Cell, Diffuse, Recurrence

What participants receive

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

  • BelinostatDrug

    Dose Escalation Phase Starting Dose: 200 mg/m2/d by vein on Days 1 and 2 of a 21 day cycle.

    Dose Expansion Starting Dose: Maximum tolerated dose from Dose Escalation Phase.

  • RituximabDrug

    Also called Rituxan

    Dose Escalation and Dose Expansion Phases: 375 mg/m2 by vein on Day 2 of a 21 day cycle.

  • CisplatinDrug

    Also called Platinol-AQ, Platinol, CDDP

    Dose Escalation and Dose Expansion Phases: 100 mg/m2 by vein on Day 2 of a 21 day cycle

  • CytarabineDrug

    Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

    Dose Escalation Phase: 2 g/m2 by vein on Day 3 of a 21 day cycle. Two doses given every 12 hours.

    Dose Expansion Phase: 2g/m2 by vein on Day 2 of a 21 day cycle. Two doses given every 12 hours.

  • DexamethasoneDrug

    Also called Decadron

    Dose Escalation and Dose Expansion Phases: 40 mg by mouth on Days 2 - 5 of a 21 day cycle.

  • CiprofloxacinDrug

    Also called Ciprofloxacin hydrochloride, Cipro

    500 mg by mouth twice daily for 10 days.

  • FluconazoleDrug

    Also called Diflucan

    100 mg by mouth daily for 10 days.

Study groups in NCT02532192
Study groupRoleWhat they receive
Belinostat + RDHAP ChemotherapyExperimentalBelinostat administered by vein on Days 1 - 2 of a 21-day cycle. Rituximab administered by vein on Day 2. Cisplatinum administered by vein on Day 2. Cytarabine administered by vein on Day 3 during the initial cohorts, and on Day 2 in the cohort of modified DHAP scheduling. Ciprofloxacin 500 mg twice daily for 10 days and Fluconazole 100 mg daily for 10 days may be utilized at the discretion of the treating physician.
Receives: Drug: Belinostat; Drug: Rituximab; Drug: Cisplatin; Drug: Cytarabine; Drug: Dexamethasone; Drug: Ciprofloxacin; Drug: Fluconazole

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Belinostat with RDHAP Chemotherapy in Participants with Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). DLT defined as an adverse event at least possibly related to study treatment:

    1. Any grade 3 or higher non-hematological toxicity possibly related to study medications per National Cancer Institute Common Terminology Criteria for Adverse Events v4.0, with exclusion of grade 3 diarrhea lasting less than 48 hours, grade 3 nausea and/or vomiting lasting less than 48 hours, grade 3 electrolyte abnormalities lasting less than 48 hours, grade 3 creatinine elevation lasting less than 48 hours
    2. Any non-hematological toxicity requiring a delay of next cycle of therapy for greater than 14 days;
    3. Grade 4 neutropenia which persists for 14 or greater days despite growth factor support.
    4. Neutropenic fever incidence closely monitored, but will not be considered a DLT due to known high rate of neutropenic fever with dose adjusted RDHAP (20 - 30%).

    Measured: 21 days

Secondary outcomes (1)

  1. Overall response Rate (ORR)

    ORR rate of Belinostat and RDHAP summarized by frequency and 95% confidence interval. Distribution of time-to-event endpoints including overall survival (OS) and progression free survival (PFS) estimated by method of Kaplan and Meier Analysis. Comparison of time-to-event endpoints by important subgroups made using the log-rank test.

    Measured: 1 year

Timeline

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

  1. First posted25 Aug 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionDec 2019 (estimated)

Why it stopped: Withdrawal of study support.

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02532192
Sponsor's protocol ID
2014-1068
Other IDs
NCI-2015-01521
Status last verified
Jan 2016
First submitted
21 Aug 2015
Last updated
6 Jan 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Belinostat, Rituximab and Cisplatin in people with Lymphoma, run by M.D. Anderson Cancer Center.

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 11 inclusion and 10 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: withdrawn, as of the sponsor's last update on 6 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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 Belinostat with RDHAP Chemotherapy in Participants with Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) (time frame: 21 days). 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 NCT02532192.

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 6 Jan 2016.

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