Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma
Azacitidine/Vorinostat/GemBuMel With Autologous Stem-Cell Transplant (SCT) in Patients With Refractory Lymphomas
2 other identifiers
interventional
61
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of azacitidine that can be given with vorinostat, gemcitabine, busulfan, and melphalan, with a stem cell transplant, and with or without rituximab. Researchers also want to learn about the safety and level of effectiveness of this combination.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2013
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2013
CompletedStudy Start
First participant enrolled
November 7, 2013
CompletedFirst Posted
Study publicly available on registry
November 14, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 22, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 22, 2017
CompletedResults Posted
Study results publicly available
January 27, 2020
CompletedJanuary 27, 2020
January 1, 2020
4 years
November 7, 2013
April 16, 2019
January 14, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Frequency of DLT
Maximum tolerated dose (MTD) of azacitidine based on DLT was defined as any Grade 4 nonhematologic and noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 3 days at peak severity. For dose finding, the continunal reassessment method was used with a target DLT probability per cohort of 25%. Azacitidine doses were chosen adaptively for sucessive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 3.
Enrollment up to day 30 post transplant for each dosing cohort
Participants With Event-free Survival (EFS)
EFS is defined as the time from transplantation to either relapse, second tumors, or death, whichever occurred first, or last contact. EFS was analzyed by the individual disease groups rather than the cohort dose levels.
Enrollment up to 100 days post transplant.
Study Arms (1)
Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan
EXPERIMENTALBusulfan test dose 32 mg/m2 by vein either as outpatient before Day -12 or as inpatient on Day -11. Busulfan pharmacokinetics performed with test dose and first dose on Day -8. Doses on Days -6 and -5 adjusted to target an AUC of 4,000 microMol.min-1. Dexamethasone 8 mg by vein twice a day from Day -11 AM to Day -2 PM. Caphosol oral rinses 30 mL four times a day used from Day -9. Oral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9. Pyridoxine 100 mg by vein or mouth three times a day from Day -1. Vorinostat 1000 mg by vein on Day -11 through Day -2. Gemcitabine loading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8. Melphalan 60 mg/m2 by vein on Days -3 and -2. Azacitidine starting dose 15 mg/ m2 by vein on Day -11. Stem cell transplant on Day 0. Patients with CD20+ tumors receive rituximab 375 mg/m2 by vein on Days -9.
Interventions
Starting dose 15 mg/ m2 by vein on Day -11.
1000 mg by vein on Day -11 through Day -2.
Loading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8.
Busulfan test dose 32 mg/m2 by vein either as outpatient before Day -12 or as inpatient on Day -11. Busulfan pharmacokinetics performed with test dose and first dose on Day -8. Doses on Days -6 and -5 adjusted to target an AUC of 4,000 microMol.min-1.
60 mg/m2 by vein on Days -3 and -2.
8 mg by vein twice a day from Day -11 AM to Day -2 PM.
Caphosol oral rinses 30 mL four times a day used from Day -9.
Oral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9.
100 mg by vein or mouth three times a day from Day -1.
375 mg/m2 by vein on Days -9.
Eligibility Criteria
You may qualify if:
- Age 15 to 65 years.
- Patients with Hodgkin's lymphoma with one or more of the following: a) Less than complete response to first-line chemotherapy. b) Relapse within 12 months of completion of first-line chemotherapy. c) Relapse within a prior irradiation field. d) Less than complete metabolic response to second-line chemotherapy. e) Second relapse or beyond. f) Extranodal disease at the time of relapse. g) Presence of B symptoms at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease. h) Bulky disease (defined as any lesion greater than 5 cm) at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease.
- Patients with non-Hodgkin's lymphoma and one or more of the following: 1. Diffuse large B-cell lymphoma with one or more of the following: a) Primary refractory disease. b) Relapse within 12 months of completion of first-line therapy. c) Secondary IPI \>1. d) Less than PR to first-line salvage chemotherapy. e) Kinetic failure after salvage chemotherapy; f) Prior treatment with 3 or more lines of therapy. g) Patients with double-hit or triple-hit NHL, in any state of the disease. 2. Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in any stage of the disease. 3. Angioimmunoblastic T-cell lymphoma (AITL) in any stage of the disease. 4. Refractory or recurrent Burkitt¹s lymphoma. 5. Any other lymphoma that is refractory or relapsed and that does not qualify for treatment protocols of higher priority.
- Adequate renal function, as defined by estimated serum creatinine clearance \>/=50 ml/min (MDRD method from National Kidney Disease Education Program, NKDEP) and/or serum creatinine \</= 1.8 mg/dL.
- Adequate hepatic function, as defined by SGOT and/or SGPT \</= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase \</= 2 x upper limit of normal.
- Adequate pulmonary function with FEV1, FVC and DLCO \>/= 50% of expected corrected for hemoglobin.
- Adequate cardiac function with left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- Zubrod performance status \<2.
- Negative Beta HCG text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
You may not qualify if:
- Patients with grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= grade 1.
- Patients with prior whole brain irradiation.
- Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/=10,000 copies/mL, or \>/= 2,000 IU/mL).
- Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
- Patients with active inflammatory bowel disease.
- Active infection requiring parenteral antibiotics.
- HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts.
- Patients having received radiation therapy in the month prior to enrollment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Nieto, Yago / Stem Cell Transplantation and Cellular Therapy
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Yago Nieto, MD, PHD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 7, 2013
First Posted
November 14, 2013
Study Start
November 7, 2013
Primary Completion
November 22, 2017
Study Completion
November 22, 2017
Last Updated
January 27, 2020
Results First Posted
January 27, 2020
Record last verified: 2020-01