A Phase 1/2 interventional study of Cyclophosphamide and Cytarabine in Adult Burkitt Lymphoma, B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma, sponsored by Northwestern University. Status unknown at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-02-21.
Sponsored by Northwestern University · Phase 1/2, Interventional, and Treatment
The purpose of this study is to evaluate the effects, good and bad of a new drug called ixazomib (also called MLN9708), when it is given along with a common treatment combination, called Dose-Adjusted EPOCH-R (DA-EPOCH-R, for short). This is a type of study called a phase I/II trial. In the phase I part, the dose of the study drug (ixazomib) will be adjusted (either up or down) to find the maximum (highest) dose that does not cause excessive (too many) harmful side effects. In the phase II part, this dose of ixazomib will be given at the maximum safe dose found in phase I. In both phase I and II, DA-EPOCH-R will be adjusted between cycles depending on how blood cell levels are affected between cycles. Ixazomib is considered investigational because it is not approved by the U.S. Food and Drug Administration (FDA). DA-EPOCH-R is a combination chemotherapy treatment developed over the last 14-15 years, and each of the drugs in this regimen is FDA-approved and considered part of the standard of care.
PRIMARY OBJECTIVES:
I. To evaluate the safety of ixazomib (ixazomib citrate) given with dose-adjusted etoposide, prednisone, vincristine (vincristine sulfate), cyclophosphamide, doxorubicin (doxorubicin hydrochloride), and rituximab (DA-EPOCH-R) in patients with aggressive, v-myc avian myelocytomatosis viral oncogene homolog (MYC)-aberrant lymphoid malignancies, and to determine the recommended phase II dose (RP2D) of the combination. (Phase I) II. To evaluate the efficacy, as measured by 12-month progression free survival (PFS), of ixazomib given with DA-EPOCH-R in patients with aggressive, MYC-aberrant lymphoid malignancies. (Phase II)
SECONDARY OBJECTIVES:
I. Further evaluate the frequency and severity of toxicity. II. Further evaluate the clinical efficacy, as measured by response rate and overall survival (OS).
III. Assess the predictive value of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scans on PFS.
TERTIARY OBJECTIVES:
I. Determine the impact of cell of origin (COO) upon response rate, PFS, and OS.
II. Assess the feasibility and outcomes of consolidation stem cell transplant (SCT).
OUTLINE: This is a phase I, dose-escalation study of ixazomib citrate followed by a phase II study.
INDUCTION:
Patients receive ixazomib citrate orally (PO) on day 1 and day 8 or 15; etoposide intravenously (IV), vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO twice daily (BID) on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5.
CENTRAL NERVOUS SYSTEM (CNS) PROPHYLAXIS:
Patients with a negative lumbar puncture (LP) receive methotrexate intrathecally (IT) once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly.
MAINTENANCE:
Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year (or as long as deriving benefit) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
976 studies on the registry are indexed under Burkitt Lymphoma; 159 are open to participants now.
This study's enrollment of 38 is close to the median of 36 across 765 interventional studies indexed under Burkitt Lymphoma.
Browse Burkitt Lymphoma studies →Northwestern University is the lead sponsor of 1,423 studies on the registry; 198 are open to participants now.
Of its 105 completed or terminated interventional studies of FDA-regulated products, 78 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have a histological diagnosis of any of the following (all stages allowed):
The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:
Female patients must meet one of the following criteria:
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity.
Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Doxorubicin Hydrochloride · Drug: Etoposide · Drug: Ixazomib Citrate · Other: Laboratory Biomarker Analysis · Drug: Methotrexate · Drug: Prednisone · Biological: Rituximab · Drug: Therapeutic Hydrocortisone · Drug: Vincristine Sulfate
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Given IT or intraventricularly
Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453
Given IV
Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex
Given IV
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213
Given PO
Also known as: MLN-9708, MLN9708
Correlative studies
Given IT or intraventricularly
Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039
Given PO
Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone
Given IV
Also known as: BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar BI 695500, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, RTXM83
Given IT or intraventricularly
Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, HYDROCORTISONE, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid
Given IV
Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate
To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R.
The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias. The dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R.
Time frame: The first 21 days of treatment
12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II)
12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability.
Time frame: Up to 12 months from initiation of treatment
Toxicity of Treatment With Ixazomib in Combination With DA-EPOCH-R
Adverse events will be assessed using CTCAE v 4.03. In general grading will be as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death.
Time frame: Assessed at the beginning each cycle with up to 6 cycles of induction treatment and up to 13 cycles of maintenance treatment (1 cycle =21 days) and at approximately 21 days after the last treatment.
Overall Survival (OS)
OS will be defined as freedom from death by any cause and measured from time of treatment initiation and completion of follow up or death from any cause.
Time frame: Up to approximately 30 months
Response Rate
Anti-tumor activity will be defined as the detection of SD (Stable Disease), Partial Response (PR), or CR (Complete Remission) by CT or PET/CT scan, and/or resolution of marrow-only involvement. CR and PR will each be assessed according to the Revised Response Criteria for Malignant Lymphoma. Assessments will be performed after cycles 2 and 6, then at the discretion of the investigator. In general: CR-Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms PR-At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease should be observed. SD-fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease
Time frame: After 2 cycles, then after 6 cycles and then at the discretion of the investigator for up to 13 maintenance cycles (1 cycle = 21 days)
Assess the Predictive Value of FDG-PET/CT Scans on PFS
Patients will be categorized as either FDG-PET (+) or (-) at interim and end-of treatment imaging.
Time frame: Up to 1 year after treatment stopped
Determine the Impact of Cell of Origin (COO) Upon Response Rate, PFS, and OS
Impact of COO defined as germinal center B-cell (GCB) and non-GCB via the Hans algorithm upon response rate, PFS, and OS (applicable only to patients with DLBCL).
Time frame: Up to 1 year
Consolidation SCT (Stem Cell Transplant)
Feasibility and outcomes of consolidation SCT will be assessed. Patients will be grouped by whether consolidative SCT was performed in first remission, with PFS compared across groups (SCT vs. non-SCT).
Time frame: Up to 1 year
The study opened to accrual on Aug 24, 2015 with the first patient being enrolled and starting treatment on 10.28.2015. The study closed to any further accrual on October 1sts 2019 with 38 patients enrolled on study. The study closed prior to reaching full accrual goal of up to 55 patients.
| Milestone | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) |
|---|---|---|---|
| Started | 1 | 36 | 1 |
| Reached first evaluable response | 1 | 34 | 1 |
| Complete 6 cycles | 1 | 30 | 1 |
| Completed | 1 | 30 | 1 |
| Not completed | 0 | 6 | 0 |
| Milestone | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) |
|---|---|---|---|
| Started | 1 | 21 | 1 |
| Started maintenance treatment | 1 | 21 | 1 |
| Completed | 1 | 21 | 1 |
| Not completed | 0 | 0 | 0 |
| Milestone | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) |
|---|---|---|---|
| Started | 1 | 32 | 1 |
| Completed | 1 | 29 | 1 |
| Not completed | 0 | 3 | 0 |
| Withdrew: Still in follow up | 0 | 3 | 0 |
The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias. The dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R.
| mg | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
|---|---|
| To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R. | 3 |
12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability.
| probability (%) of patients alive | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
|---|---|
| 12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II) | 75.84 (62.50 to 92.03) |
Adverse events will be assessed using CTCAE v 4.03. In general grading will be as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death.
Results for this outcome have not been posted.
OS will be defined as freedom from death by any cause and measured from time of treatment initiation and completion of follow up or death from any cause.
Results for this outcome have not been posted.
Anti-tumor activity will be defined as the detection of SD (Stable Disease), Partial Response (PR), or CR (Complete Remission) by CT or PET/CT scan, and/or resolution of marrow-only involvement. CR and PR will each be assessed according to the Revised Response Criteria for Malignant Lymphoma. Assessments will be performed after cycles 2 and 6, then at the discretion of the investigator. In general: CR-Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms PR-At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease should be observed. SD-fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease
Results for this outcome have not been posted.
Patients will be categorized as either FDG-PET (+) or (-) at interim and end-of treatment imaging.
Results for this outcome have not been posted.
Impact of COO defined as germinal center B-cell (GCB) and non-GCB via the Hans algorithm upon response rate, PFS, and OS (applicable only to patients with DLBCL).
Results for this outcome have not been posted.
Feasibility and outcomes of consolidation SCT will be assessed. Patients will be grouped by whether consolidative SCT was performed in first remission, with PFS compared across groups (SCT vs. non-SCT).
Results for this outcome have not been posted.
Collected over Adverse events were collected at the beginning of each cycle for up to 6 induction cycles and up to 13 maintenance cycles (1 cycle = 21 days) and 21 days after the last study treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | 6/38 (15.8%) | 20/38 (52.6%) | 38/38 (100%) |
| Event | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
|---|---|
| Febrile NeutropeniaBlood and lymphatic system disorders | 7/38 |
| CholecystitisInfections and infestations | 1/38 |
| Lung infectionInfections and infestations | 1/38 |
| Esophageal perforationGastrointestinal disorders | 1/38 |
| Thromboembolic eventVascular disorders | 1/38 |
| duodenitisInfections and infestations | 1/38 |
| Spinal fracture (lumbar)Injury, poisoning and procedural complications | 1/38 |
| SepsisInfections and infestations | 1/38 |
| COPD ExacerbationRespiratory, thoracic and mediastinal disorders | 1/38 |
| parainfluenza 3Infections and infestations | 1/38 |
| Event | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
|---|---|
| AnemiaBlood and lymphatic system disorders | 38/38 |
| Lymphocyte count decreasedInvestigations | 38/38 |
| Platelet count decreasedInvestigations | 38/38 |
| HypoalbuminemiaMetabolism and nutrition disorders | 37/38 |
| FatigueGeneral disorders | 35/38 |
| HypertensionVascular disorders | 34/38 |
| HypocalcemiaMetabolism and nutrition disorders | 34/38 |
| White blood cell decreasedInvestigations | 34/38 |
| HypokalemiaMetabolism and nutrition disorders | 33/38 |
| Neutrophil count decreasedInvestigations | 33/38 |
| Age, Categorical(Participants) | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 25 | 0 | 25 |
| >=65 years | 1 | 11 | 1 | 13 |
| Sex: Female, Male(Participants) | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) | Total |
|---|---|---|---|---|
| Female | 0 | 11 | 0 | 11 |
| Male | 1 | 25 | 1 | 27 |
| Ethnicity (NIH/OMB)(Participants) | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 1 |
| Not Hispanic or Latino | 1 | 35 | 1 | 37 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 3 | 0 | 3 |
| White | 1 | 33 | 1 | 35 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
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Studies of the drug tested here: Ixazomib