Advanced CancersPhase 1/2NCT01983969
Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma
A Phase 1/2 study testing Azacitidine, Vorinostat and Gemcitabine in people with Advanced Cancers and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Advanced Cancers, Lymphoma
- What is being tested?
- Azacitidine, Vorinostat and Gemcitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2013to 22 Nov 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 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Azacitidine/Vorinostat/GemBuMel With Autologous Stem-Cell Transplant (SCT) in Patients With Refractory Lymphomas
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.
Read the detailed description
Study Groups:
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
- Advanced Cancers, Lymphoma
- Being tested
- Azacitidine, Vorinostat, Gemcitabine, Busulfan, Melphalan
- Keywords
- Advanced Cancers, Lymphoma, Recurrent Hodgkin's, non-Hodgkin's lymphoma, Stem cell transplant, Azacitidine, 5-azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine, Vorinostat, SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza, Gemcitabine
- Medical subject headings
- Lymphoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5-azacytidine, 5-aza, Vidaza, 5-AZC
Starting dose 15 mg/ m2 by vein on Day -11.
VorinostatDrug
Also called SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
1000 mg by vein on Day -11 through Day -2.
GemcitabineDrug
Also called Gemcitabine Hydrochloride, Gemzar
Loading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8.
BusulfanDrug
Also called Busulfex, Myleran
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.
MelphalanDrug
Also called Alkeran
60 mg/m2 by vein on Days -3 and -2.
DexamethasoneDrug
Also called Decadron
8 mg by vein twice a day from Day -11 AM to Day -2 PM.
CaphosolOther
Caphosol oral rinses 30 mL four times a day used from Day -9.
GlutamineDrug
Also called Enterex, Glutapak-10, NutreStore, Resource
Oral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9.
PyridoxineDrug
100 mg by vein or mouth three times a day from Day -1.
RituximabDrug
Also called Rituxan
375 mg/m2 by vein on Days -9.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan | Experimental | 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. Receives: Drug: Azacitidine; Drug: Vorinostat; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Drug: Dexamethasone; Other: Caphosol; Drug: Glutamine; Drug: Pyridoxine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Enrollment up to 100 days post transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2013 (estimated)
- Study start7 Nov 2013
- Primary completion22 Nov 2017
- Study completion22 Nov 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 Advanced CancersStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yago Nieto, MD, PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01983969
- Sponsor's protocol ID
- 2013-0186
- Other IDs
- NCI-2014-01025
- Status last verified
- Jan 2020
- First submitted
- 7 Nov 2013
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azacitidine/Vorinostat/GemBuMel With Autologous Stem-Cell Transplant (SCT) in Patients With Refractory Lymphomas
- ClinicalTrials.gov ID
- NCT01983969
- Acronym / sponsor ID
- 2013-0186
- Conditions
- Advanced Cancers, Lymphoma
- Keywords
- Advanced Cancers, Lymphoma, Recurrent Hodgkin's, non-Hodgkin's lymphoma, Stem cell transplant, Azacitidine, 5-azacytidine, 5-aza
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 7 Nov 2013 (actual)
- Primary completion
- 22 Nov 2017 (actual)
- Study completion
- 22 Nov 2017 (actual)
- First posted
- 14 Nov 2013 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Groups:
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan | Experimental | Drug: Azacitidine, Drug: Vorinostat, Drug: Gemcitabine, Drug: Busulfan, Drug: Melphalan, Drug: Dexamethasone, Other: Caphosol, Drug: Glutamine, Drug: Pyridoxine, Drug: RituximabBusulfan 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. |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| AzacitidineAlso: 5-azacytidine, 5-aza, Vidaza, 5-AZCStarting dose 15 mg/ m2 by vein on Day -11. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| VorinostatAlso: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza1000 mg by vein on Day -11 through Day -2. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| GemcitabineAlso: Gemcitabine Hydrochloride, GemzarLoading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| BusulfanAlso: Busulfex, MyleranBusulfan 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. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| MelphalanAlso: Alkeran60 mg/m2 by vein on Days -3 and -2. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| DexamethasoneAlso: Decadron8 mg by vein twice a day from Day -11 AM to Day -2 PM. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| CaphosolCaphosol oral rinses 30 mL four times a day used from Day -9. | Other | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| GlutamineAlso: Enterex, Glutapak-10, NutreStore, ResourceOral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| Pyridoxine100 mg by vein or mouth three times a day from Day -1. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
| RituximabAlso: Rituxan375 mg/m2 by vein on Days -9. | Drug | Azacitidine + Vorinostat + Gemcitabine + Busulfan + Melphalan |
Primary outcome
Frequency of DLT
Time frame: Enrollment up to day 30 post transplant for each dosing cohort
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.
Participants With Event-free Survival (EFS)
Time frame: Enrollment up to 100 days post transplant.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Advanced Cancers
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
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.
Yago Nieto, MD, PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Azacitidine, Vorinostat and Gemcitabine in people with Advanced Cancers and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
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 8 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 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 27 Jan 2020). 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?
Frequency of DLT (time frame: Enrollment up to day 30 post transplant for each dosing cohort). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2020.