This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. A cycle of therapy is 21 days. Stage 1 was a dose-escalation stage. During Stages 2-4, patients are treated at the MTD or maximum tested dose at which multiple DLTs are not observed during Stage 1.
Completed
Phase 1/Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| SL-401 | Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Relapse/Refractory Acute Myeloid Leukemia | Experimental | Intervention: SL-401 |
|
| Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) | Experimental | Intervention: SL-401 |
|
Stage 1
Inclusion Criteria:
1. The patient has a diagnosis of AML or BPDCN according to WHO classification (AML;
excluding acute promyelocytic leukemia [APL, FAB M3]) or confirmed by hematopathology
(BPDCN)
2. The patient must meet one of the following (a) or (b) or (c):
1. Has evidence of persistent or recurrent AML in the peripheral blood and/or bone
marrow that is refractory to, or has relapsed from, their most recent prior line
of treatment.
- A prior line of treatment is considered an induction regimen if it involves
an approved or investigational cytotoxic chemotherapy agent, biological
agent, and/or hypomethylating agent administered alone or in a combination
regimen, with the intent to induce robust cytoreduction (i.e., CR).
- The previous induction regimen may have been a SCT with intent to induce a
CR.
- Consolidation and/or maintenance (including SCT) may have been given in
CR/CRi, but are not counted as a line of treatment.
- Hydroxyurea will not be considered a prior line of treatment.
2. Has previously untreated AML and is considered to be at high risk for disease
progression and/or is unlikely to derive more than transient benefit from
standard therapy by having at least one of the following:
- Treatment-related AML, except if it is associated with favorable
cytogenetics (e.g., inversion 16, t(16;16), t(8;21), t(15;17)).
- AML with antecedent hematological disease (e.g., myelodysplastic syndrome
(MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for stem
cell transplantation (SCT) in their current disease state.
3. Has histological and/or cytological evidence of BPDCN in the peripheral blood,
bone marrow, spleen, lymph nodes, skin, and/or other sites that is either
previously untreated or is persistent/recurrent following prior treatment for
BPDCN.
3. The patient is ≥ 18 years old.
4. The patient has an ECOG performance score (PS) of 0-2.
5. The patient has adequate baseline organ function, including cardiac, renal, and
hepatic function:
- Left ventricular ejection fraction (LVEF) ≥ 40% as measured by MUGA scan or 2-D
ECHO within 28 days prior to start of therapy and no clinically significant
abnormalities on a 12-lead ECG
- Serum creatinine ≤ 1.5 mg/dl
- Serum albumin ≥ 3.0 g/dl
- Bilirubin ≤ 1.5 mg/dl
- AST and ALT ≤ 2.5 times the upper limit of normal (ULN)
6. If the patient is a woman of child bearing potential (WOCBP), she has had a negative
serum or urine pregnancy test within 1 week prior to treatment.
7. The patient has signed informed consent prior to initiation of any study-specific
procedures or treatment.
8. The patient is able to adhere to the study visit schedule and other protocol
requirements, including follow-up for survival assessment.
Inclusion Criteria:
1. The patient has a diagnosis of AML or BPDCN according to WHO classification (AML;
excluding acute promyelocytic leukemia [APL, FAB M3]) or confirmed by hematopathology
(BPDCN)
2. The patient must meet one of the following (a) or (b) or (c):
1. Has evidence of persistent or recurrent AML in the peripheral blood and/or bone
marrow that is refractory to, or has relapsed from, their most recent prior line
of treatment.
- A prior line of treatment is considered an induction regimen if it involves
an approved or investigational cytotoxic chemotherapy agent, biological
agent, and/or hypomethylating agent administered alone or in a combination
regimen, with the intent to induce robust cytoreduction (i.e., CR).
- The previous induction regimen may have been a SCT with intent to induce a
CR.
- Consolidation and/or maintenance (including SCT) may have been given in
CR/CRi, but are not counted as a line of treatment.
- Hydroxyurea will not be considered a prior line of treatment.
2. Has previously untreated AML and is considered to be at high risk for disease
progression and/or is unlikely to derive more than transient benefit from
standard therapy by having at least one of the following:
- Treatment-related AML, except if it is associated with favorable
cytogenetics (e.g., inversion 16, t(16;16), t(8;21), t(15;17)).
- AML with antecedent hematological disease (e.g., myelodysplastic syndrome
(MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for SCT
in their current disease state.
3. Has histological and/or cytological evidence of BPDCN in the peripheral blood,
bone marrow, spleen, lymph nodes, skin, and/or other sites that is either
previously untreated or is persistent/recurrent following prior treatment for
BPDCN.
3. The patient is ≥ 18 years old.
4. The patient has an ECOG performance score (PS) of 0-2.
5. The patient has adequate baseline organ function, including cardiac, renal, and
hepatic function:
- Left ventricular ejection fraction (LVEF) ≥ 40% as measured by MUGA scan or 2-D
ECHO within 28 days prior to start of therapy and no clinically significant
abnormalities on a 12-lead ECG
- Serum creatinine ≤ 1.5 mg/dl
- Serum albumin ≥ 3.0 g/dl
- Bilirubin ≤ 1.5 mg/dl
- AST and ALT ≤ 2.5 times the upper limit of normal (ULN)
6. If the patient is a woman of child bearing potential (WOCBP), she has had a negative
serum or urine pregnancy test within 1 week prior to treatment.
7. The patient has signed informed consent prior to initiation of any study-specific
procedures or treatment.
8. The patient is able to adhere to the study visit schedule and other protocol
requirements, including follow-up for survival assessment.
9. The patient (male and female) agrees to use acceptable contraceptive methods for the
duration of time on the study, and continue to use acceptable contraceptive methods
for 2 months after the last infusion of SL-401.
Exclusion Criteria:
1. The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB M3).
2. The patient has persistent clinically significant toxicities Grade ≥ 2 from previous
chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests (as
mandated in the inclusion criteria)).
3. The patient has received treatment with chemotherapy, wide-field radiation, or
biologic therapy within 14 days of study entry.
4. The patient has received treatment with another investigational agent within 14 days
of study entry.
5. The patient has previously received treatment with SL-401.
6. The patient has an active malignancy and/or cancer history (excluding AML, BPDCN, or
antecedent MDS) that may confound the assessment of the study endpoints. Patients with
a past cancer history (within 2 years of entry) with substantial potential for
recurrence and/or ongoing active malignancy must be discussed with the Sponsor before
study entry. Patients with the following neoplastic diagnoses are eligible:
non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia,
organ-confined prostate cancer with no evidence of progressive disease.
7. The patient has clinically significant cardiovascular disease (e.g., uncontrolled or
any NYHA Class 3 or 4 congestive heart failure, uncontrolled angina, history of
myocardial infarction or stroke within 6 months of study entry, uncontrolled
hypertension or clinically significant arrhythmias not controlled by medication).
8. The patient has uncontrolled, clinically significant pulmonary disease (e.g., COPD,
pulmonary hypertension) that in the opinion of the investigator would put the patient
at significant risk for pulmonary complications during the study.
9. The patient has known active or suspected CNS leukemia. If suspected, CNS leukemia
should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
10. The patient is receiving immunosuppressive therapy - with the exception of low-dose
prednisone (≤ 10 mg/day) - for treatment or prophylaxis of graft-versus-host disease
(GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for
GVHD, the treatment(s) must have been discontinued at least 14 days prior to study
treatment and there must be no evidence of Grade ≥ 2 GVHD.
11. The patient has uncontrolled intercurrent illness including, but not limited to,
uncontrolled infection, DIC, or psychiatric illness/social situations that would limit
compliance with study requirements.
12. The patient is pregnant or breast feeding.
13. The patient has known positive status for human immunodeficiency virus (HIV) active or
chronic Hepatitis B or Hepatitis C.
14. The patient is oxygen-dependent.
15. The patient has any medical condition which in the opinion of the investigator places
the patient at an unacceptably high risk for toxicities.
Stage 2
BPDCN and AML patients will be grouped separately.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Primary Outcome Measures include Efficacy and Safety |
| Time Frame: | Please refer to the Study Completion date |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Stemline Therapeutics, Inc. |
April 7, 2020
