LymphomaPhase 1NCT01421173
Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
A Phase 1 study testing Vorinostat, Gemcitabine and Busulfan in people with 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 vorinostat that can be given with gemcitabine, busulfan, and melphalan with a stem cell transplant. Researchers also want to learn about the safety and level of effectiveness of this combination. Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Vorinostat, Gemcitabine and Busulfan
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Sep 2015
- 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 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 12 to 65 years
- Patients with primary refractory or recurrent non-Hodgkin's lymphoma (NHL) or HL that do not qualify for treatment protocols of higher priority.
- Patients with double-hit NHL, in any state of the disease.
- Patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in any state of the disease.
- Angioimmunoblastic T-cell lymphoma (AITL) in any stage of the disease.
- Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL.
Show all 11Show fewer
- Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal.
- Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (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 diffusing capacity of lung for carbon monoxide (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.
- Active infection requiring parenteral antibiotics
- HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts
- Patients having received radiation therapy in the month prior to enrollment.
- Patients with a cQT longer than 500 ms
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: Vorinostat (SAHA) Combined With High-Dose Gemcitabine, Busulfan, and Melphalan With Autologous Hematopoietic Cell Support for Patients With Relapsed or Refractory Lymphoid Malignancies
The goal of this clinical research study is to find the highest tolerable dose of vorinostat that can be given with gemcitabine, busulfan, and melphalan with a stem cell transplant. Researchers also want to learn about the safety and level of effectiveness of this combination.
Busulfan and melphalan are designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die.
Read more
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan and melphalan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan or melphalan.
Vorinostat is designed to open up the DNA and allow greater access to drugs that bind to DNA, such as gemcitabine, busulfan and melphalan.
Read the detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be enrolled in a group of at least 3 participants to begin receiving the study drugs.
The dose of the study drugs you receive will depend on when you enrolled in this study. If no intolerable side effects occur in your group, researchers will continue to enroll participants at the next dose level until either the vorinostat reaches the dose level currently used alone without stem cell transplant, or the highest tolerable dose of this drug is found. The dose that you receive will remain the same throughout this study.
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 -11 (11 days before your stem cells are returned to your body) and the test dose will be given on Day -10.
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.
If you receive the busulfan test dose as an outpatient:
On Days -12, -11, and -10, 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.
You will be admitted to the hospital on Day -9.
If you receive the busulfan test dose as an inpatient:
On Days -13, -12, and -11, 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.
You will be admitted to the hospital on Day -11.
Study Drug Administration (for all patients):
In stem cell transplant, 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. These drugs are used to help decrease the risk of side effects in the mouth and throat.
On Day -8 through Day -2, you will take vorinostat by mouth, with food.
On Day -8, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and busulfan by vein over 3 hours.
On Days -8, -7, -6, and -5, you will receive busulfan by vein over 3 hours.
On Day -3, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and melphalan by vein over 30 minutes.
On Day -2, you will receive melphalan by vein over 30 minutes.
On Day -1, you will rest.
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.
If you have a B-cell cancer, you will receive rituximab (a treatment used for certain lymphomas or chronic lymphocytic leukemia) by vein over 3-6 hours as part of standard of care, on Days +1 and +8.
As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin 1 time a day starting on Day +5 until your blood cell levels return to normal.
Study Tests:
On Day -1, you will have an electrocardiogram (ECG) to check your heart function.
About 30-100 days after the transplant, you will have lung function tests.
About 100 days after the transplant:
- Blood (about 4 teaspoons) will be drawn 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.
- You will have a CT scan of the neck, chest, abdomen, and pelvis to check the status of the disease.
- If the doctor thinks it is needed, you will have a PET scan to check the status of the disease.
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. 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 80 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Lymphoma
- Being tested
- Vorinostat, Gemcitabine, Busulfan, Melphalan, Stem Cell Infusion
- Keywords
- Lymphoma, Lymphoid malignancies, Relapsed, Refractory, Autologous hematopoietic cell support, Stem cell infusion, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Vorinostat, SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza, Busulfan, Busulfex, Myleran, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Melphalan
- Medical subject headings
- Lymphoma, Recurrence, Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
Starting dose: 200 mg by mouth on Days -8 to -2.
GemcitabineDrug
Also called Gemcitabine Hydrochloride, Gemzar
Starting dose: 2175 mg/m2 by vein on Days -8 and -3. This includes the gemcitabine 75 mg/m2 loading dose.
BusulfanDrug
Also called Busulfex, Myleran
AUC: 4,000 micrometer (microM).min/day, or 105 mg/m2/day) on Days -8 to -5.
Pharmacokinetics will be performed with the first dose of 32 mg/m2 by vein on Day -8. The doses on Days -6 and -5 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5.
MelphalanDrug
Also called Alkeran
60 mg/m2 by vein on Days -3 and -2.
Stem Cell InfusionProcedure or surgery
Infusion of stem cells by vein on Day 0.
RituximabDrug
Also called Rituxan
375 mg/m2 on days +1 and +8 for patients with CD20+ tumors.
G-CSFDrug
Also called Filgrastim, NeupogenTM
5 mcg/kg/day (rounded up the nearest vial) subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
PaliferminDrug
Also called Kepivance
60 mcg/kg by vein daily for 6 doses. Three doses administrated prior to start chemo (24 hours must elapse between the last dose and first therapeutic dose of chemo) and three doses after the last chemo starting on day 0.
Dexamethasone acetateDrug
Also called Decadron
8 mg by vein twice a day from day -8 AM to day -2 PM.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat + GemBuMel | Experimental | Vorinostat 200 mg by mouth on Days -8 to -2. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion. Remaining dose is 10 mg/m2/min on Day -8 and -3. Busulfan pharmacokinetics (PK) will be performed with the first dose of 105 mg/m2 by vein on Day -8. The doses of days -6 and -5 will be subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. In the event that PK adjusting were not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5. Melphalan 60 mg/m2 by vein on Days -2 and -3. Stem cells by vein over about 30-60 minutes on Day 0. Rituximab 375 mg/m2 on days +1 and +8 for cluster of differentiation antigen 20 (CD20+) tumors. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented. Palifermin 60 mcg/kg by vein daily for 6 doses starting on Day 0. Dexamethasone 8 mg by vein twice a day from day -8 AM to day -2 PM. Receives: Drug: Vorinostat; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Procedure: Stem Cell Infusion; Drug: Rituximab; Drug: G-CSF; Drug: Palifermin; Drug: Dexamethasone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Dose of Vorinostat for combination with Gemcitabine/Busulfan/Melphalan (GemBuMel) based on Dose Limiting Toxicity (DLT)
No more than 2 patients enrolled at one time in new dose level, until toxicities of at least 1 of those are assessed \& determined not to be DLT, no more patients enrolled at new dose level. Dose escalation of vorinostat starts at level 1a (200 mg/day) and Gemcitabine (2175 mg/m2/day). If level tolerable, dose proceeds from level 2a (300 mg) to level 11a (1000 mg) at increase of 100 mg per level. If level 1a were not tolerable, i.e., greater than 20% DLTs (determined by Continual Reassessment Method (CRM)), a decreased dose of gemcitabine (level 1b 1875 mg/m2) assigned and vorninostat escalation would be up to level 5b (600 mg) at increase of 100 mg per level instead.
Dose limiting toxicity (DLT) is defined as any grade 4 non-hematological, non-infectious toxicity attributable to the preparative regimen, or any grade 3 mucositis or skin toxicity that lasts more than 3 days at peak severity, or any grade 4 mucositis or skin toxicity of any duration.
Measured: About 100 days after the transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 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
- NCT01421173
- Sponsor's protocol ID
- 2011-0407
- Other IDs
- NCI-2011-02891
- Status last verified
- Nov 2015
- First submitted
- 18 Aug 2011
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Nieto Y, Valdez BC, Thall PF, Ahmed S, Jones RB, Hosing C, Popat U, Shpall EJ, Qazilbash M, Gulbis A, Anderlini P, Alousi A, Shah N, Bashir Q, Liu Y, Oki Y, Hagemeister F, Fanale M, Dabaja B, Pinnix C, Champlin R, Andersson BS. Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas. Biol Blood Marrow Transplant. 2015 Nov;21(11):1914-20. doi: 10.1016/j.bbmt.2015.06.003. Epub 2015 Jun 11.
PubMed 26071868
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vorinostat (SAHA) Combined With High-Dose Gemcitabine, Busulfan, and Melphalan With Autologous Hematopoietic Cell Support for Patients With Relapsed or Refractory Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT01421173
- Acronym / sponsor ID
- 2011-0407
- Conditions
- Lymphoma
- Keywords
- Lymphoma, Lymphoid malignancies, Relapsed, Refractory, Autologous hematopoietic cell support, Stem cell infusion, Hodgkin's lymphoma, non-Hodgkin's lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 22 Aug 2011 (estimated)
- Results
- Not posted in the source record
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 vorinostat that can be given with gemcitabine, busulfan, and melphalan with a stem cell transplant. Researchers also want to learn about the safety and level of effectiveness of this combination.
Busulfan and melphalan are designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan and melphalan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan or melphalan.
Vorinostat is designed to open up the DNA and allow greater access to drugs that bind to DNA, such as gemcitabine, busulfan and melphalan.
Detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be enrolled in a group of at least 3 participants to begin receiving the study drugs.
The dose of the study drugs you receive will depend on when you enrolled in this study. If no intolerable side effects occur in your group, researchers will continue to enroll participants at the next dose level until either the vorinostat reaches the dose level currently used alone without stem cell transplant, or the highest tolerable dose of this drug is found. The dose that you receive will remain the same throughout this study.
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 -11 (11 days before your stem cells are returned to your body) and the test dose will be given on Day -10.
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.
If you receive the busulfan test dose as an outpatient:
On Days -12, -11, and -10, 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.
You will be admitted to the hospital on Day -9.
If you receive the busulfan test dose as an inpatient:
On Days -13, -12, and -11, 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.
You will be admitted to the hospital on Day -11.
Study Drug Administration (for all patients):
In stem cell transplant, 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. These drugs are used to help decrease the risk of side effects in the mouth and throat.
On Day -8 through Day -2, you will take vorinostat by mouth, with food.
On Day -8, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and busulfan by vein over 3 hours.
On Days -8, -7, -6, and -5, you will receive busulfan by vein over 3 hours.
On Day -3, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and melphalan by vein over 30 minutes.
On Day -2, you will receive melphalan by vein over 30 minutes.
On Day -1, you will rest.
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.
If you have a B-cell cancer, you will receive rituximab (a treatment used for certain lymphomas or chronic lymphocytic leukemia) by vein over 3-6 hours as part of standard of care, on Days +1 and +8.
As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin 1 time a day starting on Day +5 until your blood cell levels return to normal.
Study Tests:
On Day -1, you will have an electrocardiogram (ECG) to check your heart function.
About 30-100 days after the transplant, you will have lung function tests.
About 100 days after the transplant:
- Blood (about 4 teaspoons) will be drawn 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.
- You will have a CT scan of the neck, chest, abdomen, and pelvis to check the status of the disease.
- If the doctor thinks it is needed, you will have a PET scan to check the status of the disease.
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. 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 80 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat + GemBuMel | Experimental | Drug: Vorinostat, Drug: Gemcitabine, Drug: Busulfan, Drug: Melphalan, Procedure: Stem Cell Infusion, Drug: Rituximab, Drug: G-CSF, Drug: Palifermin, Drug: Dexamethasone acetateVorinostat 200 mg by mouth on Days -8 to -2. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion. Remaining dose is 10 mg/m2/min on Day -8 and -3. Busulfan pharmacokinetics (PK) will be performed with the first dose of 105 mg/m2 by vein on Day -8. The doses of days -6 and -5 will be subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. In the event that PK adjusting were not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5. Melphalan 60 mg/m2 by vein on Days -2 and -3. Stem cells by vein over about 30-60 minutes on Day 0. Rituximab 375 mg/m2 on days +1 and +8 for cluster of differentiation antigen 20 (CD20+) tumors. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented. Palifermin 60 mcg/kg by vein daily for 6 doses starting on Day 0. Dexamethasone 8 mg by vein twice a day from day -8 AM to day -2 PM. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Age 12 to 65 years
- Patients with primary refractory or recurrent non-Hodgkin's lymphoma (NHL) or HL that do not qualify for treatment protocols of higher priority.
- Patients with double-hit NHL, in any state of the disease.
- Patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in any state of the disease.
- Angioimmunoblastic T-cell lymphoma (AITL) in any stage of the disease.
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.
- Active infection requiring parenteral antibiotics
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 |
|---|---|---|
| VorinostatAlso: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, ZolinzaStarting dose: 200 mg by mouth on Days -8 to -2. | Drug | Vorinostat + GemBuMel |
| GemcitabineAlso: Gemcitabine Hydrochloride, GemzarStarting dose: 2175 mg/m2 by vein on Days -8 and -3. This includes the gemcitabine 75 mg/m2 loading dose. | Drug | Vorinostat + GemBuMel |
| BusulfanAlso: Busulfex, MyleranAUC: 4,000 micrometer (microM).min/day, or 105 mg/m2/day) on Days -8 to -5. Pharmacokinetics will be performed with the first dose of 32 mg/m2 by vein on Day -8. The doses on Days -6 and -5 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5. | Drug | Vorinostat + GemBuMel |
| MelphalanAlso: Alkeran60 mg/m2 by vein on Days -3 and -2. | Drug | Vorinostat + GemBuMel |
| Stem Cell InfusionInfusion of stem cells by vein on Day 0. | Procedure or surgery | Vorinostat + GemBuMel |
| RituximabAlso: Rituxan375 mg/m2 on days +1 and +8 for patients with CD20+ tumors. | Drug | Vorinostat + GemBuMel |
| G-CSFAlso: Filgrastim, NeupogenTM5 mcg/kg/day (rounded up the nearest vial) subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented. | Drug | Vorinostat + GemBuMel |
| PaliferminAlso: Kepivance60 mcg/kg by vein daily for 6 doses. Three doses administrated prior to start chemo (24 hours must elapse between the last dose and first therapeutic dose of chemo) and three doses after the last chemo starting on day 0. | Drug | Vorinostat + GemBuMel |
| Dexamethasone acetateAlso: Decadron8 mg by vein twice a day from day -8 AM to day -2 PM. | Drug | Vorinostat + GemBuMel |
Primary outcome
Recommended Dose of Vorinostat for combination with Gemcitabine/Busulfan/Melphalan (GemBuMel) based on Dose Limiting Toxicity (DLT)
Time frame: About 100 days after the transplant
No more than 2 patients enrolled at one time in new dose level, until toxicities of at least 1 of those are assessed \& determined not to be DLT, no more patients enrolled at new dose level. Dose escalation of vorinostat starts at level 1a (200 mg/day) and Gemcitabine (2175 mg/m2/day). If level tolerable, dose proceeds from level 2a (300 mg) to level 11a (1000 mg) at increase of 100 mg per level. If level 1a were not tolerable, i.e., greater than 20% DLTs (determined by Continual Reassessment Method (CRM)), a decreased dose of gemcitabine (level 1b 1875 mg/m2) assigned and vorninostat escalation would be up to level 5b (600 mg) at increase of 100 mg per level instead. Dose limiting toxicity (DLT) is defined as any grade 4 non-hematological, non-infectious toxicity attributable to the preparative regimen, or any grade 3 mucositis or skin toxicity that lasts more than 3 days at peak severity, or any grade 4 mucositis or skin toxicity of any duration.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2015.
- Derived from this study: PubMed 26071868Nieto Y, Valdez BC, Thall PF, Ahmed S, Jones RB, Hosing C, Popat U, Shpall EJ, Qazilbash M, Gulbis A, Anderlini P, Alousi A, Shah N, Bashir Q, Liu Y, Oki Y, Hagemeister F, Fanale M, Dabaja B, Pinnix C, Champlin R, Andersson BS. Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas. Biol Blood Marrow Transplant. 2015 Nov;21(11):1914-20. doi: 10.1016/j.bbmt.2015.06.003. Epub 2015 Jun 11.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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 study testing Vorinostat, Gemcitabine and Busulfan in people with 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 11 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 18 Nov 2015. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Recommended Dose of Vorinostat for combination with Gemcitabine/Busulfan/Melphalan (GemBuMel) based on Dose Limiting Toxicity (DLT) (time frame: About 100 days after the transplant). 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 NCT01421173, which also lists 1 linked publication.
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 18 Nov 2015.