LymphomaPhase 1/2NCT02589145
Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype
A Phase 1/2 study testing Lenalidomide, Vorinostat and Gemcitabine 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 lenalidomide that can be given in combination 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
- Lymphoma
- What is being tested?
- Lenalidomide, Vorinostat and Gemcitabine
- 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
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2016to 8 Apr 2019
- 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 15-65
- Patients with ABC (determined by immunohistochemistry using the Hans algorithmI) DLBCL with primary refractory disease, relapse <12 months after initial therapy, secondary International Prognostic Index (IPI) >1, less than partial response to salvage treatment or exposure to >3 salvage regimens
- Adequate renal function, as defined by an estimated serum creatinine clearance >/= 50 ml/min (MDRD method) and/or serum creatinine </= 1.8 mg/dL
- Adequate hepatic function (SGOT and/or SGPT </= 3 x ULN; bilirubin and ALP </= 2 x ULN
- Adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) >/= 50%
- Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
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- ECOG performance status <2
- Negative Beta HCG in woman with child-bearing potential
- All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
Who cannot join
- Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1
- Prior whole brain irradiation
- 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 CD4 counts
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- Radiation therapy in the month prior to enrollment
- History of arterial thromboembolic events in the past 3 months and of venous thromboembolic events in the past month
- History of hypersensitivity of lenalidomide or thalidomide
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
The goal of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination 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 effectiveness of this combination.
Read the detailed description
Central Venous Catheter:
Many of the drugs given in this study and the stem cell transplant will be given by vein through a central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of lenalidomide based on when you join this study. Up to 3 dose levels of lenalidomide 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 lenalidomide is found.
All participants will receive the same dose level of vorinostat, gemcitabine, busulfan, rituximab, and melphalan. However, if the first group of participants have any bad 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 levels changes over time. This information will be used to decide the next dose needed to match 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.
Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan 11 times. 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, you will receive the standard fixed dose of busulfan.
You will also receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat either during the 2 days before you are admitted (inpatient) or during the 3 days before you are admitted (outpatient) You may ask the study staff about the risks of palifermin.
Study Drug Administration (all patients):
Beginning on Day -8, you will swish caphosol and glutamine liquids 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 Days -9 through Day -2, you will take lenalidomide and vorinostat by mouth, with food.
If you the doctor thinks it is needed, you will receive rituximab 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 4½ hours.
On Days -8 through Day -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 under your skin 1 time each day starting on Day +5 until your blood cell levels return to normal. You may ask the study staff about the risks of filgrastim.
Pregnancy Tests:
If you can become pregnant and have regular menstrual cycles, blood (up to 2 teaspoons) will be drawn for a pregnancy test on the following schedule:
- Within 10-14 days and within 24 hours before your first dose of lenalidomide, even if you have not had a menstrual period due to treatment or you have only had 1 menstrual period in the past 24 months.
- One (1) time each week for 4 weeks, then every 4 weeks while taking lenalidomide.
- Four (4) weeks after you stop taking lenalidomide.
If you have irregular menstrual cycles, you will have pregnancy tests every week for the first 28 days, then every 14 days while you are taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 14 and 28 days after you have stopped taking lenalidomide.
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 computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease.
- 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.
This is an investigational study. Lenalidomide is FDA approved and commercially available for the treatment of multiple myeloma (MM) and myelodysplastic syndrome (MDS). Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphoma and certain types of leukemia. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma (CTCL). Gemcitabine is FDA approved and commercially available for the treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, and ovarian cancer. Busulfan is FDA approved and commercially available for the treatment of chronic myeloid leukemia (CML). Melphalan is FDA approved and commercially available for the treatment of lymphoma.
The use of these study drugs in combination to treat DLBCL is considered investigational. The study doctor can explain how the study drugs are designed to work.
Up to 30 participants will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Lymphoma
- Being tested
- Lenalidomide, Vorinostat, Gemcitabine, Busulfan, Melphalan
- Keywords
- Blood And Marrow Transplantation, Diffuse large B-cell lymphoma, DLBCL, Busulfan, Busulfex, Myleran, Lenalidomide, CC-5013, Revlimid, Vorinostat, SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Melphalan, Alkeran, Rituximab
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called CC-5013, Revlimid
Dose Escalation Phase Starting dose of Lenalidomide: 50 mg by mouth on Days -9 to -2.
Dose Expansion Phase Starting Dose: Maximum tolerated dose from Phase I.
VorinostatDrug
Also called SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
1000 mg by mouth on Days -9 to -2.
GemcitabineDrug
Also called Gemcitabine Hydrochloride, Gemzar
Gemcitabine administered as a loading dose of 75 mg/m2 by vein on Day -8 and 2775 mg by vein on Day -3.
BusulfanDrug
Also called Busulfex, Myleran
Busulfan test dose administered by vein either as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently 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.
RituximabDrug
Also called Rituxan
Patients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient.
DexamethasoneDrug
Also called Decadron
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
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 four times a day, swished, gargled and swallowed started on Day -8.
PyridoxineDrug
100 mg by vein or mouth three times a day from Day -1
EnoxaparinDrug
Also called Lovenox Injection
40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
Stem Cell TransplantProcedure or surgery
Also called SCT
Stem cell transplant performed on Day 0.
PaliferminDrug
Also called Kepivance
Palifermin per departmental standard of care with 3 doses to be administered prior to starting chemotherapy and 3 doses starting on day 0.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT | Experimental | Vorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy.
Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3.
Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
Melphalan administered at 60 mg/m2 on days -3 and -2.
Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient.
Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8.
Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3. Receives: Drug: Lenalidomide; Drug: Vorinostat; Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Drug: Rituximab; Drug: Dexamethasone; Drug: Caphosol; Drug: Glutamine; Drug: Pyridoxine; Drug: Enoxaparin; Procedure: Stem Cell Transplant; Drug: Palifermin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting > 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
Measured: Enrollment up to day 30 post transplant for each dosing cohort
Event-free Survival (EFS)
Determined the 2-year event-free survival (EFS)
Measured: Up to 2 years post transplant
Secondary outcomes (5)
Overall Survival (OS)
Assessed the 2-year overall survival (OS)
Measured: Up to 2 years post transplant
Complete Remission (CR) Rate
Determined complete remission (CR) rate
Measured: Up to 2 years post transplant
Overall Remission Rate (ORR)
Determined overall remission rate (ORR) rate
Measured: Up to 2 years post transplant
Toxicity Profile
Determined the toxicity profile
Measured: Up to 2 years post transplant
Pharmacodynamic Studies
Evaluated IRF4, SPIB, STAT1, p-STAT1, CARD11, I-kappa-Kinase-beta and p-I-kappa-Kinase-beta in PBMNC pre- and post-treatment (at baseline and on day -1).
Measured: Up to 2 years post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study start22 Jun 2016
- Primary completion8 Apr 2019
- Study completion8 Apr 2019
Why it stopped: Closed due to very slow accrual
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 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Yago Nieto, MD, PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02589145
- Sponsor's protocol ID
- 2015-0558
- Other IDs
- NCI-2015-01938
- Status last verified
- Nov 2019
- First submitted
- 26 Oct 2015
- Last updated
- 13 Dec 2019
- 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 13 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype
- ClinicalTrials.gov ID
- NCT02589145
- Acronym / sponsor ID
- 2015-0558
- Conditions
- Lymphoma
- Keywords
- Blood And Marrow Transplantation, Diffuse large B-cell lymphoma, DLBCL, Busulfan, Busulfex, Myleran, Lenalidomide, CC-5013
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed due to very slow accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- 22 Jun 2016 (actual)
- Primary completion
- 8 Apr 2019 (actual)
- Study completion
- 8 Apr 2019 (actual)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Posted 13 Dec 2019
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 lenalidomide that can be given in combination 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 effectiveness of this combination.
Detailed description
Central Venous Catheter:
Many of the drugs given in this study and the stem cell transplant will be given by vein through a central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of lenalidomide based on when you join this study. Up to 3 dose levels of lenalidomide 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 lenalidomide is found.
All participants will receive the same dose level of vorinostat, gemcitabine, busulfan, rituximab, and melphalan. However, if the first group of participants have any bad 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 levels changes over time. This information will be used to decide the next dose needed to match 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.
Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan 11 times. 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, you will receive the standard fixed dose of busulfan.
You will also receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat either during the 2 days before you are admitted (inpatient) or during the 3 days before you are admitted (outpatient) You may ask the study staff about the risks of palifermin.
Study Drug Administration (all patients):
Beginning on Day -8, you will swish caphosol and glutamine liquids 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 Days -9 through Day -2, you will take lenalidomide and vorinostat by mouth, with food.
If you the doctor thinks it is needed, you will receive rituximab 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 4½ hours.
On Days -8 through Day -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 under your skin 1 time each day starting on Day +5 until your blood cell levels return to normal. You may ask the study staff about the risks of filgrastim.
Pregnancy Tests:
If you can become pregnant and have regular menstrual cycles, blood (up to 2 teaspoons) will be drawn for a pregnancy test on the following schedule:
- Within 10-14 days and within 24 hours before your first dose of lenalidomide, even if you have not had a menstrual period due to treatment or you have only had 1 menstrual period in the past 24 months.
- One (1) time each week for 4 weeks, then every 4 weeks while taking lenalidomide.
- Four (4) weeks after you stop taking lenalidomide.
If you have irregular menstrual cycles, you will have pregnancy tests every week for the first 28 days, then every 14 days while you are taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 14 and 28 days after you have stopped taking lenalidomide.
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 computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease.
- 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.
This is an investigational study. Lenalidomide is FDA approved and commercially available for the treatment of multiple myeloma (MM) and myelodysplastic syndrome (MDS). Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphoma and certain types of leukemia. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma (CTCL). Gemcitabine is FDA approved and commercially available for the treatment of non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, and ovarian cancer. Busulfan is FDA approved and commercially available for the treatment of chronic myeloid leukemia (CML). Melphalan is FDA approved and commercially available for the treatment of lymphoma.
The use of these study drugs in combination to treat DLBCL is considered investigational. The study doctor can explain how the study drugs are designed to work.
Up to 30 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 |
|---|---|---|
| Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT | Experimental | Drug: Lenalidomide, Drug: Vorinostat, Drug: Gemcitabine, Drug: Busulfan, Drug: Melphalan, Drug: Rituximab, Drug: Dexamethasone, Drug: Caphosol, Drug: Glutamine, Drug: Pyridoxine, Drug: Enoxaparin, Procedure: Stem Cell Transplant, Drug: PaliferminVorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy. Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3. Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. Melphalan administered at 60 mg/m2 on days -3 and -2. Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient. Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8. Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3. |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age 15-65
- Patients with ABC (determined by immunohistochemistry using the Hans algorithmI) DLBCL with primary refractory disease, relapse <12 months after initial therapy, secondary International Prognostic Index (IPI) >1, less than partial response to salvage treatment or exposure to >3 salvage regimens
- Adequate renal function, as defined by an estimated serum creatinine clearance >/= 50 ml/min (MDRD method) and/or serum creatinine </= 1.8 mg/dL
- Adequate hepatic function (SGOT and/or SGPT </= 3 x ULN; bilirubin and ALP </= 2 x ULN
- Adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) >/= 50%
Key exclusion criteria (9 listed)
- Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1
- Prior whole brain irradiation
- 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 |
|---|---|---|
| LenalidomideAlso: CC-5013, RevlimidDose Escalation Phase Starting dose of Lenalidomide: 50 mg by mouth on Days -9 to -2. Dose Expansion Phase Starting Dose: Maximum tolerated dose from Phase I. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| VorinostatAlso: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza1000 mg by mouth on Days -9 to -2. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| GemcitabineAlso: Gemcitabine Hydrochloride, GemzarGemcitabine administered as a loading dose of 75 mg/m2 by vein on Day -8 and 2775 mg by vein on Day -3. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| BusulfanAlso: Busulfex, MyleranBusulfan test dose administered by vein either as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| MelphalanAlso: Alkeran60 mg/m2 by vein on days -3 and -2. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| RituximabAlso: RituxanPatients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| DexamethasoneAlso: Decadron8 mg by vein twice a day from Day -8 AM to Day -2 PM. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| CaphosolCaphosol oral rinses 30 mL four times a day used from Day -8. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| GlutamineAlso: Enterex, Glutapak-10, NutreStore, ResourceOral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| Pyridoxine100 mg by vein or mouth three times a day from Day -1 | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| EnoxaparinAlso: Lovenox Injection40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| Stem Cell TransplantAlso: SCTStem cell transplant performed on Day 0. | Procedure or surgery | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
| PaliferminAlso: KepivancePalifermin per departmental standard of care with 3 doses to be administered prior to starting chemotherapy and 3 doses starting on day 0. | Drug | Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Enrollment up to day 30 post transplant for each dosing cohort
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting > 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
Event-free Survival (EFS)
Time frame: Up to 2 years post transplant
Determined the 2-year event-free survival (EFS)
5 secondary outcomes
Overall Survival (OS)
Time frame: Up to 2 years post transplant
Complete Remission (CR) Rate
Time frame: Up to 2 years post transplant
Overall Remission Rate (ORR)
Time frame: Up to 2 years post transplant
Toxicity Profile
Time frame: Up to 2 years post transplant
Pharmacodynamic Studies
Time frame: Up to 2 years post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 1/2 study testing Lenalidomide, Vorinostat and Gemcitabine 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 10 inclusion and 9 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: stopped early, as of the sponsor's last update on 13 Dec 2019. 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 13 Dec 2019). 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?
Maximum Tolerated Dose (MTD) (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 13 Dec 2019.