Diffuse, Large B-cell Lymphoma Clinical Trial
Official title:
Phase I/II Study of MLN4924 Alone Followed by Dose-Adjusted EPOCH-Rituximab + MLN4924 With Gene Expression Profiling and Mutational Analysis in Relapsed/Refractory de Novo Diffuse Large B-Cell Lymphoma
Background:
- MLN4924 is an experimental cancer drug. It may help kill lymphoma cells and make them more
sensitive to chemotherapy. EPOCH R is a combination chemotherapy drug. It has been effective
in treating some cases of large B-cell lymphoma. This research will look at two things. The
first is the effect of MLN4924 on its own in treating large B-cell lymphoma. The second is
the safe dose and effect of MLN4924 and EPOCH-R in combination when treating large B-cell
lymphoma.
Objectives:
- To study how MLN4924 affects large B-cell lymphoma tumors.
- To compare the effects of MLN 4924 alone and MLN4924 plus standard EPOCH-R chemotherapy.
Eligibility:
- Individuals at least 18 years of age who have large B-cell lymphoma that will be treated
with chemotherapy.
Design:
- Participants will be screened with a medical history and physical exam. They will also
have blood and urine tests, tumor samples, and imaging studies.
- Participants will receive MLN4924 for a maximum of six 21-day cycles of treatment. Each
cycle involves a dose of MLN4924 twice a week for 2 weeks, followed by a 1-week rest
period. Participants will be monitored with frequent blood tests and imaging studies.
- Participants who do not benefit from MLN4924 alone will have MLN4924 along with EPOCH-R
chemotherapy for up to six cycles of treatment.
Background:
- Diffuse large B-cell lymphomas (DLBCL) have been molecularly sub-classified into
germinal center like B-cell (GCB) and activated B-cell like (ABC) DLBCL.
- Clinically, the ABC subtype has a significantly higher rate of drug resistance and lower
survival. The ABC subtype has constitutive activation of the NF-KappaB pathway which may
account for the drug resistance.
- The ability of NF-KappaB to inhibit responses to cancer therapeutic agents may also
contribute to the refractory clinical behavior of ABC subtype, and inhibition of
NF-KappaB can synergize with chemotherapy to kill tumor cells.
- Because a phase II randomized design is not clinically or technically practical at this
early stage to address the scientific endpoints, we have designed a novel endpoint based
on relative efficacy of DA-EPOCH-R + MLN 4924 (DA-EPOCH-RN) in ABC and GCB DLBCL. Based
on our study that shows that survival of relapsed ABC and GCB DLBCL are comparable and
poor following initial R-CHOP, we hypothesize that significantly improved survival of
ABC compared to GCB DLBCL after DA-EPOCH-RN is strongly indicative of preferential
activity of MLN4924 in ABC DLBCL.
Objectives:
- Assess response of MLN4924 in relapsed/refractory DLBCL
- Assess toxicity and safe tolerated dose of MLN4924 and DA-EPOCH-R
- Assess difference in response (CR/PR) and OS in ABC and GCB DLBCL
Eligibility:
- Relapsed/refractory de novo DLBCL greater than or equal to 18 years.
- No PMBL DLBCL
- No patients with active CNS lymphoma.
- No pregnant or breast-feeding women.
- Adequate organ function (as defined in protocol).
Study Design:
- This is a single center with a sequential treatment design. The study is divided into
two parts (A and B). Clinical end points are to assess the activity of MLN4924 alone
(Part A) and in combination with DA-EPOCH-R (Part B), and to assess the toxicity and MTD
of DA-EPOCH-RN.
- In Part A, MLN4924 will be given alone for 6 cycles.
- In Part B, MLN4924 will be initially escalated to determine the maximum tolerated dose
(MTD) in combination with DA-EPOCH-R at dose levels (to be determined) and schedule
every 21 days. Responding or stable patients may receive up to 6 cycles of DAEPOCH-RN.
- Patients will be restaged every 2 cycles during treatment, and every 3, 4 and 6 months
during years one, two and three respectively, thereafter. Standard response criteria
will be applied.
- A total of 56 patients will be enrolled depending on the relative differences in
response observed between the ABC and GCB subtypes to MLN4924.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00924326 -
CAR T Cell Receptor Immunotherapy for Patients With B-cell Lymphoma
|
Phase 1/Phase 2 |