Phase 1
N=11
Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) and Alemtuzumab for People With Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL)
T-Cell Lymphoma Relapsed · Adult T-Cell Leukemia (ATL) · Peripheral T-Cell Lymphoma (PTCL) · Cutaneous T Cell Lymphoma (CTCL) · T-Cell Prolymphocytic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT02689453 ↗Enrolled (actual)
11
Serious AEs
27.3%
Results posted
Apr 2022
Primary outcome: Primary: Maximum Tolerated Dose (MTD) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) — 2 mcg/kg/dose
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- IL-15 plus (Biological); alemtuzumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jun 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) |
2 | — |
| PRIMARY Number of Dose-limiting Toxicities (DLTs) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) Administered With 3 Times Per Week Intravenous (IV) Alemtuzumab |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to Subcutaneous (s.c. rhIL-15) by Grade Who Have Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL)Cancer |
1; 1; 1; 0; 0; 1 | — |
| SECONDARY Number of Participants With a Clinical Response |
1; 0; 1; 0; 1; 1 | — |
| SECONDARY Progression Free Survival (PFS) |
78; 83; 138 | — |
| SECONDARY Percentages of Circulating Lymphocytes (T and NK Cells) and the T-cell Subsets |
— | — |
| SECONDARY Plasma Levels of Pro-inflammatory Cytokines |
— | — |
Summary
Background:
Adult T-cell leukemia (ATL) is a rare blood cancer. Researchers want to see if a combination of two drugs - recombinant human interleukin 15 (rhIL-15) and alemtuzumab - is a better treatment for ATL.
Objectives:
To test if giving rhIL-15 combined with alemtuzumab improves the outcome of therapy for ATL. Also, to determine the safe dose of this combination and identify side effects and effects on the immune system.
Eligibility:
Adults 18 years and older with chronic or acute ATL who have not been helped by other treatments.
Design:
Participants will be screened with tests that are mostly part of their usual cancer care. They will sign a separate consent form for this.
Weeks 1 and 2: Participants will have a total of 10 visits. They will:
* Get rhIL-15 under the skin by needle.
* Have a physical exam and vital signs measured.
* Give blood samples.
* Answer questions about their health and their medicines.
Week 3: Participants will stay in the clinic. They will:
* Get alemtuzumab infusions in a vein through a small catheter on days 1, 2, 3, and 5.
* Take medicines to decrease side effects.
* Have a computed tomography (CT) scan to evaluate the treatment.
* Have a physical exam and vital signs measured.
* Give blood samples.
Answer questions about their health and medicines.
Weeks 4, 5, and 6 will repeat week 3, without the CT scan. Some patients will just have outpatient visits these weeks.
After treatment, participants will have follow-up visits every few months for up to 2 years. At these visits, participants will give blood samples and have CT scans.
Eligibility Criteria
- INCLUSION CRITERIA:
Inclusion Criteria
- Age greater than or equal to 18 years; no upper age limit.
- Patients diagnosed with a leukemia or lymphoma as follows:
- Chronic or acute leukemia forms of Human T-cell lymphotropic virus type 1 (HTLV-1) associated adult T-cell leukemia;
- Peripheral T-cell lymphoma (angioimmunoblastic, hepatosplenic, or not otherwise specified); or,
- Cutaneous T-cell lymphoma stage III or IV with circulating monoclonal cells (B1 or B2) and/or erythrodermia (T4)
- T-cell prolymphocytic leukemia (T-PLL)
NOTE: Diagnosis must be validated by the Pathology Department, National Cancer Institute (NCI).
-Patients must have measurable or evaluable disease.
NOTE: All patients with greater than 10% abnormal cluster of differentiation 4 (CD4+) homogeneous cluster of differentiation 3 (CD3) low strongly cluster of differentiation 25 (CD25+) expressing cells, or greater than 5% Szary cells/T-PLL, among the peripheral blood mononuclear cells (PBMCs) in the peripheral blood will be deemed to have evaluable disease.
- Abnormal T cells must be cluster of differentiation 52 (CD52+) as assessed by flow cytometry or immunohistochemistry.
- Patients must have a life expectancy of greater than or equal to 2 months.
- Patients must have been refractory or relapsed following front line therapy for Adult T-cell Leukemia (ATL); those with cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) who have cluster of differentiation 30 (CD30+) disease must have progressed during or after treatment with brentuximab vedotin, or are unable to receive treatment due to allergy or intolerance.
- Patients must have recovered to less than grade 1 or to baseline from toxicity of prior chemotherapy or biologic therapy and must not have had major surgery, chemotherapy, radiation or biologic therapy within 2 weeks prior to beginning treatment. NOTE: Exceptions to this include events not considered to place the subject at unacceptable risk of participation in the opinion of the PI (e.g., alopecia).
- Carbon monoxide diffusing capacity alveolar volume (DLCO/VA) and forced expiratory volume (FEV) 1.0 > 50% of predicted on pulmonary function tests.
- Adequate laboratory parameters, as follows:
- Serum creatinine of less than or equal to 1.5 x the upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the upper limit of normal
- Absolute neutrophil count greater than or equal to 1,500/mm^3 and platelets greater than or equal to 100,000/mm^3.
- Eastern Cooperative Oncology Group (ECOG) less than or equal to 1.
- Patients must be able to understand and sign an Informed Consent Form.
- All patients must use adequate contraception during participation in this trial and for 4 months following completing therapy.
EXCLUSION CRITERIA
- Patients who have received any systemic corticosteroid therapy within 4 weeks prior to the start of therapy, or 12 weeks if given to treat graft versus host disease (GVHD), with the exception of physiological replacement doses of cortisone acetate or equivalent.
- Patients who have undergone allogeneic stem cell transplantation and have required systemic treatment for GVHD (including but not limited to oral or parenteral corticosteroids, ibrutinib, and extracorporeal phototherapy) within the last 12 weeks
- Clinical evidence of (parenchymal or meningeal) central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, a magnetic resonance imaging (MRI) scan of the brain and lumbar puncture should be done to confirm.
- Documented human immunodeficiency virus (HIV), active bacterial infections, active or chronic hepatitis B, hepatitis C.
- Positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) negative) or a fully resolved acute hepatitis B infection is not an exclusion criterion.
- If hepatitis C antibody test is positiv
Data sourced from ClinicalTrials.gov (NCT02689453). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.