Trial Title:
Study of Mogamulizumab With DA-EPOCH in Patients With Aggressive T Cell Lymphoma
NCT ID:
NCT05996185
Condition:
T Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Prednisone
Cyclophosphamide
Doxorubicin
Etoposide
Vincristine
Mogamulizumab
Conditions: Keywords:
Relapsed
Refractory
Adult T-Cell Leukemia/Lymphoma
Cutaneous T-cell lymphoma
Mycosis Fungoides/Sézary syndrome
DA-EPOCH
Mogamulizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab
Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.
Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Mogamulizumab
Description:
Mogamulizumab is a humanized monoclonal antibody directed against C-C chemokine receptor
4 (CCR4) with potential anti-inflammatory and antineoplastic activities. Mogamulizumab
selectively binds to and blocks the activity of CCR4, which may inhibit CCR4-mediated
signal transduction pathways and, so, chemokine-mediated cellular migration and
proliferation of T cells, and chemokine-mediated angiogenesis.
Arm group label:
Mogamulizumab + DA-EPOCH
Other name:
Poteligeo
Intervention type:
Drug
Intervention name:
DA-EPOCH Protocol
Description:
EPOCH is an intensive chemotherapy regimen intended for treatment of aggressive
non-Hodgkin's lymphoma.
Arm group label:
Mogamulizumab + DA-EPOCH
Other name:
dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone
Summary:
Single- arm Phase II study evaluating the combination of mogamulizumab (MOGA) added on
top of standard of care dose adjusted EPOCH (DA-EPOCH) in patients with newly diagnosed
or relapsed/refractory (for CTCL only) aggressive T cell lymphoma including patients with
Adult T-cell leukemia/lymphoma (ATLL).
Detailed description:
This is a single arm, open label, multicenter phase 2 study of DA-EPOCH and Mogamulizumab
in patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T-cell
lymphomas including ATLL and transformed Mycosis Fungoides/Sézary syndrome (MF/SS). The
hypothesis is that this combination is effective and will produce a CR rate of 80%.
DA-EPOCH and Mogamulizumab will be administered for 6 cycles and depending on the
histology, consolidative strategies including SCT will be considered. Response
assessments will occur at pre-specified intervals. Dose adjustments for specific
toxicities with drugs are detailed in the protocol. Based on statistical analysis, a
maximum of 36 patients will need to be accrued to evaluate for disease response based on
historical control.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male/female patients who are at least 18 years of age on the day of signing informed
consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma
(TNHL) will be enrolled in this study.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 unless
compromised by lymphoma with anticipated benefit from chemotherapy as determined and
documented by the investigator.
3. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including but not
limited to:
- Peripheral T-cell lymphoma not otherwise specified (PTCL nos)
- Angioimmunoblastic T-cell lymphoma (AITL)
- Anaplastic large-cell lymphoma (ALCL)
- Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary
syndrome patients for whom multi-agent chemotherapy is indicated
- Transformed mycosis fungoides/Sezary syndrome
- Enteropathy-associated T-cell lymphoma (EATL)
- Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
- Hepatosplenic T- cell lymphomas
- Gamma delta T cell lymphomas
- Adult T-cell lymphoma leukemia (ATLL)
- T-prolymphocytic leukemia with nodal or visceral involvement
4. Prior therapy- patients with aggressive T cell lymphoma may have received one cycle
of CHOP, CHOEP or EPOCH before enrollment, if necessary, to control the disease.
5. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target
lesion ≥ 1.5 cm
6. A female patient is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR
- A woman of childbearing potential (WOCBP) - see Appendix 4 for definition of
WOCBP - must have a negative serum or urine pregnancy test during screening and
must agree to follow instructions for using acceptable contraception (Appendix
5) from the time of signing consent, and at least 180 days (6 months) after her
final dose of mogamulizumab.
7. A male patient must agree to use a contraception as detailed in Appendix 5 of this
protocol during the treatment period and for at least at least 180 days (6 months)
after her final dose of mogamulizumab and refrain from donating sperm during this
period.
8. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of
protocol-indicated treatment unless compromised by disease involvement of bone
marrow, spleen, or liver as determined and documented by the investigator.
9. Patients previously treated with anti-CD4 antibody or alemtuzumab are eligible
provided their CD4+ cell counts are ≥ 200/mm.
Exclusion Criteria:
1. Has received prior systemic anti-cancer therapy including investigational agents ≤ 3
weeks prior to first dose of study treatment on Cycle 1, Day 1. Skin directed
treatments, including topicals and radiation within 2 weeks of study treatment.
However, patients with rapidly progressive malignant disease may be enrolled prior
to this period after discussion with the sponsor investigator.
2. Has received radiotherapy within 2 weeks of start of study treatment. Patients must
have recovered from all radiation-related toxicities, and not have had radiation
pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of
radiotherapy) to non-CNS disease.
3. If patient received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study
treatment.
4. Patients on any immunomodulatory drug for concomitant or intercurrent conditions
other than T-cell lymphoma or who have received any of these agents within 4 weeks
of treatment, including but not limited to the following, will be excluded: low dose
or oral methotrexate; azathioprine; iv immunoglobulin; low dose or oral
cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; leflunomide;
adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β IL-2 and
natalizumab. . Concurrent use of topical steroids or therapies for CTCL is allowed
as indicated in the protocol.
5. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test
within 72 hours of treatment start. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.
6. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg,FluMist®) are live attenuated vaccines and are not allowed.
7. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study treatment.
Note: Patients who have entered the follow-up phase of an investigational study may
participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
8. Active uncontrolled infection requiring systemic therapy (patients must be afebrile
for ≥ 48 hours and off antibiotics prior to treatment). If fever is attributed to
tumor fever (B symptom) then these criteria would not apply.
9. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA)
functional classification III-IV heart failure (Appendix 4).
10. Known active CNS metastases and/or carcinomatous meningitis. Patients with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to first dose of study treatment.
11. Diagnosed with a malignancy, not treated under the study (hormonal therapy for
breast or prostate cancer excepted), in the past 2 years. However, patients with
nonmelanoma skin cancers, melanoma in situ, localized cancer of the prostate with
current prostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical
carcinoma in situ or ductal/lobular carcinoma in situ of the breast with in the past
2 years may enroll as long as there is no current evidence of disease.
12. Known severe hypersensitivity (≥Grade 3) to mogamulizumab and/or any of its
excipients and /or EPOCH or any of its excipients.
13. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is
required unless mandated by local health authority.
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.
15. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
16. Has a known history of active TB (Bacillus Tuberculosis).
17. Prior allogeneic stem cell transplant within last 2 years or active graft vs. host
disease (GVHD).
18. Known active autoimmune disease will be excluded if the disease requires active
medical treatment. (For example, Graves' disease; systemic lupus erythematosus;
rheumatoid arthritis; Crohn's disease; psoriasis).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Yale Cancer Center, Clinical Trials Office
Address:
City:
New Haven
Zip:
06510
Country:
United States
Contact:
Last name:
Tatiana Khorokhorina, BSN, RN, MBA
Phone:
203-859-0593
Email:
tatiana.khorokhorina@yale.edu
Investigator:
Last name:
Tarsheen Sethi, MD
Email:
Principal Investigator
Start date:
October 2024
Completion date:
November 2027
Lead sponsor:
Agency:
Yale University
Agency class:
Other
Collaborator:
Agency:
Kyowa Kirin, Inc.
Agency class:
Industry
Source:
Yale University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05996185
