LymphomaPhase 1/2NCT02701673
Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma
A Phase 1/2 study testing Busulfan, Caphosol and Glutamine in people with Lymphoma, run by M.D. Anderson Cancer Center.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be given in combination with azacitidine, gemcitabine, busulfan, and melphalan to patients who are scheduled to have a stem cell transplant. Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Busulfan, Caphosol and Glutamine
- 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
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2016to Jun 2019
- Phase
- Phase 1/2
- 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 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 15-65
- Patients with: 2. 1. DLBCL with one of the following: 2.1.1. Primary refractory (no CR to 1st line). 2.1.2. High-risk relapse (CR1 <6 months, secondary IPI >1, high LDH). 2.1.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.2. Hodgkin's with one of the following: 2.2.1. Primary refractory (no CR to 1st line or PD within 3 months). 2.2.2. High-risk relapse (CR1 <1 year, extranodal relapse, B symptoms). 2.2.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.3. T-NHL with one of the following: 2.3.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.3.2. Nonresponsive (SD/PD) to >/= 1 line of salvage. 2.4. Burkitt's or lymphoblastic lymphoma with one of the following: 2.4.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.4.2. Refractory to at least 1 line of salvage (SD/PD).
- Adequate renal function, as defined by estimated serum creatinine clearance >/= 50 ml/min and/or serum creatinine </= 1.8 mg/dL.
- Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal (ULN); bilirubin and ALP </= 2 x ULN.
- Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb) >/= 50%.
- Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- PS <2.
- Negative Beta human chorionic gonadotropin (HCG) in woman with child-bearing potential.
Who cannot join
- Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1.
- Prior whole brain irradiation.
- Corrected QT interval (QTc) longer than 500 ms.
- 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 receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts.
- Radiation therapy in the month prior to enrollment.
About this study
The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be given in combination with azacitidine, gemcitabine, busulfan, and melphalan to patients who are scheduled to have a stem cell transplant. If you have diffuse large B-cell lymphoma (DLBCL), you will also receive rituximab. Researchers also want to learn about the safety and effectiveness of this combination.
Read the detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of belinostat based on when you join this study. Up to 5 dose levels of belinostat will be tested. At least 2 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 belinostat is found.
All participants will receive the same dose level of azacitidine, gemcitabine, busulfan, melphalan. All patients with DLBCL will also receive the same dose of rituximab. However, if the first group has intolerable side effects, the dose level of gemcitabine may be lowered for all other groups.
Busulfan Test Dose:
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.
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 level changes over time. This information will be used to decide the next dose needed to reach the dose 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 busulfan cannot be given to you 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.
On either Day -11 or -10, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing 11 times over the 11 hours after your test dose 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. The PK blood draws 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.
About 2 or 3 days before receiving the test dose of busulfan (depending on if you are an inpatient or outpatient), 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 (all patients):
Beginning on Day -8, you will swish 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 -9 through Day -2, you will receive belinostat continuously by vein. You will also receive azacitidine by vein on each of these days over about 30 minutes. Depending on the type of cancer you have, you will also receive rituximab by vein over 3-6 hours as part of standard care on Day -9. The study staff will tell you if you will receive rituximab.
On Day -8, you will receive gemcitabine by vein over 4½ 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 4½ 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.
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, if you are unable to follow study directions, or if you choose to leave the study early.
If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low.
Follow-Up:
About 100 days after the transplant:
- You will have a physical exam.
- Blood (about 4 teaspoons) and urine will be collected for routine tests and to check your kidney and liver function.
- If the doctor thinks it is needed, you will have a computed tomography (CT) and/or positron emission tomography (PET) scan to check the status of the disease.
- If the doctor thinks it is needed, you will 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 or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
This is an investigational study. Belinostat, busulfan, and rituximab are FDA approved and commercially available for the treatment of lymphoma. Gemcitabine is FDA approved and commercially available for the treatment of breast cancer, non-small cell lung cancer (NSCLC), ovarian cancer, and pancreatic cancer. Melphalan is FDA approved and commercially available for the treatment of multiple myeloma (MM). Azacitidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). The use of these study drugs in combination to treat lymphoma is considered investigational.
Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Lymphoma
- Being tested
- Busulfan, Caphosol, Glutamine, Pyridoxine, Belinostat
- Keywords
- Refractory or Relapsed Lymphoma, Busulfan, Busulfex, Myleran, Caphosol, Glutamine, Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X-G.I., Sympt-X, Pyridoxine, Belinostat, Azacitidine, 5-azacytidine, 5-aza, Azacytidine, Vidaza
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex, Myleran
Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
CaphosolDrug
Caphosol oral rinses 30 mL four times a day used from Day -8.
GlutamineDrug
Also called Enterex, Glutapak-10, NutreStore, Resource
Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8.
PyridoxineDrug
Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1
BelinostatDrug
Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2.
AzacitidineDrug
Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2.
GemcitabineDrug
Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3.
MelphalanDrug
Also called Alkeran
Melphalan 60 mg/m2 by vein on Days -3 and -2.
Stem Cell TransplantProcedure or surgery
Stem cell transplant performed on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Belinostat/Gem/Bu/Mel + AutoSCT | Experimental | Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1.
Caphosol oral rinses 30 mL four times a day used from Day -8. Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8.
Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1. Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2. Participants with cluster of differentiation antigen 20 (CD20+) tumors receive Rituximab 375 mg/m2 by vein on Day -9.
Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3.
Melphalan 60 mg/m2/d by vein on Day -2. Stem cell transplant by vein given on Day 0. Receives: Drug: Busulfan; Drug: Caphosol; Drug: Glutamine; Drug: Pyridoxine; Drug: Belinostat; Drug: Azacitidine; Drug: Gemcitabine; Drug: Melphalan; Procedure: Stem Cell Transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Belinostat Combined with Azacitidine and Gemcitabine/Busulfan/Melphalan (AZA-GemBuMel) in Participants with Refractory or Poor-Risk Relapsed Lymphoma
For purpose of dose-finding, "toxicity" defined as any of the following events occurring within 30 days from the start of Belinostat infusion :
- any grade 4 or 5 non-hematologic toxicity, or
- any grade 3 or 4 mucositis, or
- any grade 3 or 4 skin toxicity lasting > 5 days at peak severity
Optimal dose defined as that for which the posterior mean of Pr(toxicity within 30 days | dose) given the current data is closest to 0.30.
Measured: 30 days
Secondary outcomes (1)
Treatment Related Mortality (TRM100)
Treatment related mortality (TRM100), defined as death due to any cause without disease recurrence within 100 days post stem cell transplant (SCT).
Measured: 100 days after stem cell transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT02701673
- Sponsor's protocol ID
- 2015-0560
- Status last verified
- May 2016
- First submitted
- 2 Mar 2016
- Last updated
- 4 May 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma
- ClinicalTrials.gov ID
- NCT02701673
- Acronym / sponsor ID
- 2015-0560
- Conditions
- Lymphoma
- Keywords
- Refractory or Relapsed Lymphoma, Busulfan, Busulfex, Myleran, Caphosol, Glutamine, Enterex, Glutapak-10
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jun 2019 (estimated)
- First posted
- 8 Mar 2016 (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 belinostat that can be given in combination with azacitidine, gemcitabine, busulfan, and melphalan to patients who are scheduled to have a stem cell transplant. If you have diffuse large B-cell lymphoma (DLBCL), you will also receive rituximab. Researchers also want to learn about the safety and effectiveness of this combination.
Detailed description
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of belinostat based on when you join this study. Up to 5 dose levels of belinostat will be tested. At least 2 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 belinostat is found.
All participants will receive the same dose level of azacitidine, gemcitabine, busulfan, melphalan. All patients with DLBCL will also receive the same dose of rituximab. However, if the first group has intolerable side effects, the dose level of gemcitabine may be lowered for all other groups.
Busulfan Test Dose:
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.
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 level changes over time. This information will be used to decide the next dose needed to reach the dose 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 busulfan cannot be given to you 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.
On either Day -11 or -10, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing 11 times over the 11 hours after your test dose 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. The PK blood draws 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.
About 2 or 3 days before receiving the test dose of busulfan (depending on if you are an inpatient or outpatient), 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 (all patients):
Beginning on Day -8, you will swish 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 -9 through Day -2, you will receive belinostat continuously by vein. You will also receive azacitidine by vein on each of these days over about 30 minutes. Depending on the type of cancer you have, you will also receive rituximab by vein over 3-6 hours as part of standard care on Day -9. The study staff will tell you if you will receive rituximab.
On Day -8, you will receive gemcitabine by vein over 4½ 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 4½ 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.
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, if you are unable to follow study directions, or if you choose to leave the study early.
If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low.
Follow-Up:
About 100 days after the transplant:
- You will have a physical exam.
- Blood (about 4 teaspoons) and urine will be collected for routine tests and to check your kidney and liver function.
- If the doctor thinks it is needed, you will have a computed tomography (CT) and/or positron emission tomography (PET) scan to check the status of the disease.
- If the doctor thinks it is needed, you will 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 or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
This is an investigational study. Belinostat, busulfan, and rituximab are FDA approved and commercially available for the treatment of lymphoma. Gemcitabine is FDA approved and commercially available for the treatment of breast cancer, non-small cell lung cancer (NSCLC), ovarian cancer, and pancreatic cancer. Melphalan is FDA approved and commercially available for the treatment of multiple myeloma (MM). Azacitidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). The use of these study drugs in combination to treat lymphoma is considered investigational.
Up to 60 participants 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 |
|---|---|---|
| Belinostat/Gem/Bu/Mel + AutoSCT | Experimental | Drug: Busulfan, Drug: Caphosol, Drug: Glutamine, Drug: Pyridoxine, Drug: Belinostat, Drug: Azacitidine, Drug: Gemcitabine, Drug: Melphalan, Procedure: Stem Cell TransplantBusulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8. Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1. Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2. Participants with cluster of differentiation antigen 20 (CD20+) tumors receive Rituximab 375 mg/m2 by vein on Day -9. Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3. Melphalan 60 mg/m2/d by vein on Day -2. Stem cell transplant by vein given on Day 0. |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age 15-65
- Patients with: 2. 1. DLBCL with one of the following: 2.1.1. Primary refractory (no CR to 1st line). 2.1.2. High-risk relapse (CR1 <6 months, secondary IPI >1, high LDH). 2.1.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.2. Hodgkin's with one of the following: 2.2.1. Primary refractory (no CR to 1st line or PD within 3 months). 2.2.2. High-risk relapse (CR1 <1 year, extranodal relapse, B symptoms). 2.2.3. Refractory relapse: No response (SD or PD) to >/= 1 line of salvage. 2.3. T-NHL with one of the following: 2.3.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.3.2. Nonresponsive (SD/PD) to >/= 1 line of salvage. 2.4. Burkitt's or lymphoblastic lymphoma with one of the following: 2.4.1. Primary refractory (</= CR to 1st line or relapse within 6 months). 2.4.2. Refractory to at least 1 line of salvage (SD/PD).
- Adequate renal function, as defined by estimated serum creatinine clearance >/= 50 ml/min and/or serum creatinine </= 1.8 mg/dL.
- Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal (ULN); bilirubin and ALP </= 2 x ULN.
- Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb) >/= 50%.
Key exclusion criteria (8 listed)
- Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1.
- Prior whole brain irradiation.
- Corrected QT interval (QTc) longer than 500 ms.
- 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.
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 |
|---|---|---|
| BusulfanAlso: Busulfex, MyleranBusulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| CaphosolCaphosol oral rinses 30 mL four times a day used from Day -8. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| GlutamineAlso: Enterex, Glutapak-10, NutreStore, ResourceOral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| PyridoxinePyridoxine 100 mg by vein or mouth three times a day staring on Day -1 | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| BelinostatStarting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| AzacitidineAzacitidine 15 mg/m2/day by vein on Day -9 through Day -2. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| GemcitabineGemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| MelphalanAlso: AlkeranMelphalan 60 mg/m2 by vein on Days -3 and -2. | Drug | Belinostat/Gem/Bu/Mel + AutoSCT |
| Stem Cell TransplantStem cell transplant performed on Day 0. | Procedure or surgery | Belinostat/Gem/Bu/Mel + AutoSCT |
Primary outcome
Maximum Tolerated Dose (MTD) of Belinostat Combined with Azacitidine and Gemcitabine/Busulfan/Melphalan (AZA-GemBuMel) in Participants with Refractory or Poor-Risk Relapsed Lymphoma
Time frame: 30 days
For purpose of dose-finding, "toxicity" defined as any of the following events occurring within 30 days from the start of Belinostat infusion : 1. any grade 4 or 5 non-hematologic toxicity, or 2. any grade 3 or 4 mucositis, or 3. any grade 3 or 4 skin toxicity lasting > 5 days at peak severity Optimal dose defined as that for which the posterior mean of Pr(toxicity within 30 days | dose) given the current data is closest to 0.30.
1 secondary outcome
Treatment Related Mortality (TRM100)
Time frame: 100 days after stem cell transplant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2016.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
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
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Busulfan, Caphosol and Glutamine in people with Lymphoma, run by M.D. Anderson Cancer Center.
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 8 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: withdrawn, as of the sponsor's last update on 4 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Maximum Tolerated Dose (MTD) of Belinostat Combined with Azacitidine and Gemcitabine/Busulfan/Melphalan (AZA-GemBuMel) in Participants with Refractory or Poor-Risk Relapsed Lymphoma (time frame: 30 days). 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 4 May 2016.