Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
61 participants
INTERVENTIONAL
2013-11-07
2017-11-22
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma
NCT01129180
High-Dose Gemcitabine, Busulfan and Melphalan for Patients With Refactory Hodgkin's Disease
NCT01200329
Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma
NCT00992446
CHOEP + High Dose Therapy + Auto SCT for T-Cell Lymphoma
NCT01746173
Olaparib and High-Dose Chemotherapy in Treating Patients With Relapsed or Refractory Lymphomas Undergoing Stem Cell Transplant
NCT03259503
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
If you have been found to be eligible to take part in this study and you agree, you will be assigned to a dose level of azacitidine based on when you join this study. Up to 7 dose levels of azacitidine will be tested. At least 3 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 azacitidine is found.
All participants will receive the same dose level of vorinostat, gemcitabine, busulfan, and melphalan, and all patients with B-cell cancer will receive the same dose of rituximab. However, if the first group has bad side effects, the dose level of gemcitabine may be lowered for all other groups.
Busulfan Test Dose:
You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in your blood levels changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches your body size. You will most likely receive this as an outpatient during the week before you are admitted to the hospital. If it cannot be given as an outpatient, you will be admitted to the hospital on Day -12 (12 days before your stem cells are returned to your body) and the test dose will be given on Day -11.
About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points and will help the study doctor determine what your dose of busulfan should be on study. These blood samples will be drawn at various timepoints before you receive busulfan and over about the next 11 hours. The blood samples will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose of busulfan.
On Days -14, -13, and -12, you will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.
Study Drug Administration (for all patients):
In stem cell transplants, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive your stem cells are called plus days.
Beginning on Day -9, you will swish the liquids caphosol and glutamine in your mouth 4 times a day, for about 2 minutes each time. You will swish these liquids every day until you leave the hospital. You will swallow the glutamine. These drugs are used to help decrease the risk of side effects in the mouth and throat.
On Day -11 through Day -2, you will take vorinostat by mouth, with food. One hour later each day, you will receive azacitidine by vein over 1 hour. You will receive dexamethasone by vein 2 times each day.
If you have a B-cell cancer, you will receive rituximab (a treatment used for certain lymphomas) by vein over 3-6 hours as part of standard of care, on Day -9.
On Day -8, you will receive gemcitabine by vein over 4 ½ hours.
On Days -8, -7, -6, and -5, you will receive busulfan by vein over 2 hours.
On Day -3, you will receive gemcitabine by vein over 4 ½ hours and then melphalan by vein over 30 minutes.
On Day -2, you will receive melphalan by vein over 30 minutes.
On Day -1, you will rest (you will not receive chemotherapy).
On Day 0, you will receive your stem cells by vein over about 30-60 minutes.
You will receive 3 more doses of palifermin by vein over 15-30 seconds on Days 0, +1, and +2.
As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin 1 time each day starting on Day +5 until your blood cell levels return to normal.
Study Tests:
About 100 days after the transplant:
* You will have a physical exam.
* Blood (about 4 teaspoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, you may have a bone marrow aspiration and biopsy to check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
Length of Study:
As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are released from the hospital, you will continue as an outpatient in the Houston area to be monitored for infections and transplant-related complications.
You will be taken off study about 100 days after the transplant. You may be taken off study early if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
This is an investigational study. Azacitidine, vorinostat, gemcitabine, busulfan, melphalan, and rituximab are all FDA approved and commercially available. The use of these study drugs in combination is investigational.
Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan
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. 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.
Azacitidine
Starting dose 15 mg/ m2 by vein on Day -11.
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.
Busulfan
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.
Melphalan
60 mg/m2 by vein on Days -3 and -2.
Dexamethasone
8 mg by vein twice a day from Day -11 AM to Day -2 PM.
Caphosol
Caphosol oral rinses 30 mL four times a day used from Day -9.
Glutamine
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.
Rituximab
375 mg/m2 by vein on Days -9.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Azacitidine
Starting dose 15 mg/ m2 by vein on Day -11.
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.
Busulfan
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.
Melphalan
60 mg/m2 by vein on Days -3 and -2.
Dexamethasone
8 mg by vein twice a day from Day -11 AM to Day -2 PM.
Caphosol
Caphosol oral rinses 30 mL four times a day used from Day -9.
Glutamine
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.
Rituximab
375 mg/m2 by vein on Days -9.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. 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.
3. 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.
4. 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.
5. 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.
6. Adequate pulmonary function with FEV1, FVC and DLCO \>/= 50% of expected corrected for hemoglobin.
7. Adequate cardiac function with left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
8. Zubrod performance status \<2.
9. Negative Beta HCG text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
Exclusion Criteria
2. Patients with prior whole brain irradiation.
3. Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/=10,000 copies/mL, or \>/= 2,000 IU/mL).
4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
5. Patients with active inflammatory bowel disease.
6. Active infection requiring parenteral antibiotics.
7. HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts.
8. Patients having received radiation therapy in the month prior to enrollment.
15 Years
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
M.D. Anderson Cancer Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Yago Nieto, MD, PHD
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
University of Texas MD Anderson Cancer Center Website
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2014-01025
Identifier Type: REGISTRY
Identifier Source: secondary_id
2013-0186
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.