A Phase 1/2, open label, multicenter study to assess the safety and tolerability of durvalumab (anti-PD-L1 antibody) as monotherapy and in combination therapy in subjects with lymphoma or chronic lymphocytic leukemia. (MEDI4736-NHL-001). The *FUSION NHL 001* Study.
- Conditions
- leukemialymph node cancer1002432410025322
- Registration Number
- NL-OMON53056
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
ALL TREATMENT ARMS
1. Subject is >= 18 years of age and <= 80 years of age at the time of signing
the ICF. Subjects > 80 years of age may be included if they meet criteria
defined in the protocol.
2. Subject must understand and voluntarily sign an ICF prior to any
study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other
protocol requirements.
4. Subject has histologically confirmed and documented eligible histologies as
defined in the protocol.
5. Subject has been previously treated with at least one prior systemic
chemotherapy, immunotherapy, or chemoimmunotherapy.
6. Subject with high-risk CLL/SLL is defined by the presence of at least one of
the following factors:
a. Complex karyotype;
b. del (17p) abnormality;
c. Mutated TP53;
d. Ibrutinib-or other BTK-inhibitor failure or an inadequate tumor response
which is less than partial response;
e. Relapsed/progressive disease within 6 months of completing their last
therapy which may include investigational drug.
7. Subject is willing and able to undergo biopsy:
a. Subject with lymphoma is willing and able to undergo tumor/lymph node biopsy
(incisional/excisional or multiple core needle):
- During the Screening Period
- Any time during Cycle 2 (strongly recommended), and
- At the time of disease progression from subjects who have achieved objective
response (CR/PR) to study treatment.
b. Subject with CLL is willing and able to undergo bone marrow biopsy during
the Screening and Treatment Periods.
Material from a fine needle aspiration is not acceptable.
8. Subject who has documented active relapsed or refractory disease requiring
therapeutic intervention.
9. Subject who has measurable disease:
a. For subject with lymphoma, bi-dimensionally measurable disease on
cross-sectional imaging by computed tomography (CT) with at least one nodal or
extranodal lesion >=2.0 cm in its longest dimension.
Note: A previously irradiated lesion is ineligible to be used as a measurable
target
lesion.
b. For subject with CLL, in need of treatment as defined by IWCLL Guidelines
for the Diagnosis and Treatment of CLL (Appendix I of protocol).
Subject who has performance status of 0, 1, or 2 on the ECOG scale.
10. Subject who has life expectancy of greater than 6 months.
11. Subject who fulfills the laboratory requirements outlined in Table 6 of the
protocol.
12. Female subject of childbearing potential (FCBP1) who is sexually active
with a male must:
a. Have 2 negative pregnancy tests as verified by the investigator prior to
starting any IP therapy. They must agree to ongoing pregnancy testing during
the course of the study, and after the last dose of any IP. This applies even
if the subject practices true abstinence from heterosexual contact.
b. Use effective methods (1 highly effective and 1 additional effective
[barrier] method) of contraception from 28 days prior to starting durvalumab,
and must agree to continue using such precautions while taking durvalumab
(including dose interruptions) and for 90 days after
the last dose of durvalumab. Cessation of contraception after this point should
be discussed with a responsible physician.
The following are examples of highly effective and additional effective methods
of contraception:<b
ALL TREATMENT ARMS
1. Subject who has known or suspected central nervous system (CNS) or meningeal
involvement by lymphoma.
2. Subject who has other lymphoma histologies which are not listed on Table
3, Table 4, or Table 5 of the protocol.
a. Subject who has blastoid variants of MCL or MCL with blastoid transformation.
b. Dose Confirmation and/or Expansion Parts only:
- Transformed lymphoma or Richter's transformation
- DLBCL histology other than: not otherwise specified or T-cell/histiocyte rich.
3. Subject who has any histopathologic finding consistent with myelodysplastic
syndrome on bone marrow studies.
4. Subject who has any significant medical condition, laboratory abnormality,
or psychiatric illness that would prevent the subject from participating in the
study.
5. Subject who has any condition including the presence of laboratory
abnormalities, which places the subject at unacceptable risk if he/she were to
participate in the study.
6. Subject who has any condition that confounds the ability to interpret data
from the study.
7. Subject who has any uncontrolled inter-current illness as defined in the
protocol.
8. Subject who is concurrently enrolled in another clinical study, unless in a
follow-up period or it is an observational study.
9. Subject who has any concurrently chemotherapy, immunotherapy, biologic, or
hormonal therapy for cancer treatment.
10. Subject who has received:
a) Any systemic antilymphoma/leukemia therapy, or hematopoietic growth factors,
blood or platelets transfusions within 14 days prior to the first dose of IP
(ie, Cycle1 Day 1) and/or
b) Any radioimmunotherapy within 3 months prior to the first dose of IP (ie,
Cycle 1
Day 1).
11. Subject who has unresolved toxicities from prior anticancer therapy,
defined as having not resolved to NCI CTCAE v4.03 <= Grade 1 with the exception
of alopecia and laboratory values listed per the exclusion criteria. Subjects
with irreversible toxicity that is not reasonably
expected to be exacerbated by durvalumab or other investigational treatments
may be included (eg, hearing loss) after consultation with the sponsor's
medical monitor.
12. Subject who received any prior mAb against PD-1 or PD-L1 and/or any prior:
a. Arm A only: IMiDs (eg, lenalidomide, thalidomide);
b. Arm B only: ibrutinib or other BTK inhibitor;
c. Arms C only: bendamustine.
13. Subject who has history of organ transplant or allogeneic hematopoietic
stem cell transplantation.
14. Subject who has taken corticosteroids during the last 1 week prior to fist
dose of IP (ie,Cycle 1 Day 1), unless administered at a dose equivalent to <= 10
mg/day prednisone. See protocol for exceptions.
15. Subject who has received live, attenuated vaccine within 30 days prior to
the first dose of durvalumab (NOTE: Subjects, if enrolled, should not receive
live vaccine during the study and for 12 monhts after last dose of rituximab or
until recovery of B-cells and for 120 days after the last dose of durvalumab,
whichever is longer).
16. Subject who has undergone major surgical procedure (as defined by the
investigator) within 28 days prior to the first dose of the IP or still
recovering from prior surgery.
17. Subject who has active documented autoimmune disease prior to first dose of
durvalumab.
18. Subject who has history of
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method