Study Stopped
Withdrawal of study support.
A Phase Ib Study of Belinostat With RDHAP Chemotherapy (Dexamethasone, Cytarabine, Cisplatinum) in Adults With Relapsed or Refractory Diffuse Large B-cell Lymphoma
2 other identifiers
interventional
N/A
0 countries
N/A
Brief 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 the patient's own stem cells). The safety of the study drug will also be studied.
Trial Health
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 21, 2015
CompletedFirst Posted
Study publicly available on registry
August 25, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedJanuary 6, 2016
January 1, 2016
4 years
August 21, 2015
January 5, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (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%).
21 days
Secondary Outcomes (1)
Overall response Rate (ORR)
1 year
Study Arms (1)
Belinostat + RDHAP Chemotherapy
EXPERIMENTALBelinostat 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.
Interventions
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.
Dose Escalation and Dose Expansion Phases: 375 mg/m2 by vein on Day 2 of a 21 day cycle.
Dose Escalation and Dose Expansion Phases: 100 mg/m2 by vein on Day 2 of a 21 day cycle
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.
Dose Escalation and Dose Expansion Phases: 40 mg by mouth on Days 2 - 5 of a 21 day cycle.
500 mg by mouth twice daily for 10 days.
100 mg by mouth daily for 10 days.
Eligibility Criteria
You may qualify if:
- 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).
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Spectrum Pharmaceuticals, Inccollaborator
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jason R. Westin, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2015
First Posted
August 25, 2015
Study Start
December 1, 2015
Primary Completion
December 1, 2019
Last Updated
January 6, 2016
Record last verified: 2016-01