NCT02661022 · REGISTRY CONDITION SEARCH

SL-401 in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2024-04-17

A Phase 1/2, Open Label Study of SL-401 in Combination with Pomalidomide and Dexamethasone In Relapsed and Refractory Multiple Myeloma

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Patients With Dose-limiting Toxicities and Treatment-emergent Adverse Events

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outcome · POSTED

Number of Patients With Treatment-related Adverse Events

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outcome · POSTED

Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Progression-free Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Eligible patients will be considered for inclusion if they meet all of the following criteria. (All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.) 1. Male or female patient who is at least 18 years of age. 2. Patient has given voluntary written informed consent before performance of any study-related procedures not part of standard (non-investigational) medical care. 3. Patient has been previously diagnosed with MM based on standard criteria. 4. Patient has received: 1. At least 2 prior therapies including a proteasome inhibitor (≥ 2 cycles) and lenalidomide (≥ 2 cycles), and 2. Has achieved at least stable disease (SD) for ≥ 1 cycle of treatment on ≥ 1 prior treatment, and 3. Has demonstrated disease progression subsequent to treatment, during or within 90 days following completion of the most recent therapy. 5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2. 6. Patient has measurable disease defined as at least 1 of the following: 1. Serum M protein ≥ 0.5 /dL (≥5 g/L) 2. Urine M protein ≥ 200 mg/24 hours 3. Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65) 7. Clinical Laboratory Inclusion Criteria: The following laboratory results must be met within 14 days (or as stipulated) prior to study drug (treatment) administration: 1. Absolute neutrophil count (ANC) ≥ 1000 cells/μl (growth factor cannot be used within the previous 7 days). 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN). 3. Platelet count ≥ 50,000/μl (without platelet transfusion in the previous 7 days). 4. Total bilirubin ≤ 1.5 mg/dL. 5. Serum creatinine ≤ 2.0 mL/dL and creatinine clearance ≥ 40 mL/min (calculated by the Cockcroft-Gault Equation or per 24 hour urine collection). 6. Serum albumin ≥ 3.2 g/dL in the absence of receipt of (IV) albumin within the previous 72 hours. 7. Serum creatine phosphokinase (CPK) ≤ 2.5 × the ULN. 8. Serum calcium (corrected for albumin) level at or below the ULN range (treatment of hypercalcemia is allowed and patient may enroll if hypercalcemia returns to normal range with standard treatment). 8. Left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal as measured by multigated acquisition scan (MUGA) scan or 2-dimensional echocardiography (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG). 9. Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test prior to initiation of the SL-401 Run in Cycle (if required) and repeated with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control, 1 highly effective method and 1 additional effective method at the same time, at least 28 days before she starts taking Pomalidomide through 30 days after the last dose of Pomalidomide and 60 days after the last dose of SL-401. FCBP must also agree to ongoing pregnancy testing during the entire duration of treatment. Men must agree to use a latex or synthetic condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 60 days after the last dose of Pomalidomide or SL-401. These same patients must not donate sperm. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. All patients enrolled into this study, must agree to be registered in and must comply with all requirements of the Pomalidomide REMS(TM) program. * An FCBP is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Exclusion Criteria: Patients will be ineligible for this study if they meet any 1 of the following criteria: 1. The patient has an active malignancy and/or cancer history 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 (including superficial bladder cancer), cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease. 2. Prior therapy with SL-401 or received any investigational drug within the prior 30 days or 5 half-lives of the investigational drug, whichever is longer. 3. Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within the prior 14 days except for alkylating agents (e.g., melphalan) within the prior 28 days. 4. Pomalidomide (POM)-refractory disease (i.e., non-responsive to prior POM \[either as monotherapy or in combination\] or relapse/progressive disease within 60 days of prior POM (either as monotherapy or in combination). Prior POM exposure is permitted, provided the patient's MM is not considered POM-refractory as defined above. 5. Primary refractory MM defined as disease that is non-responsive in patients that have never achieved at least stable disease or better with any therapy. 6. Any \> grade 1 (according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], v.4.03) adverse reaction unresolved from previous treatments or not readily managed and controlled with supportive care. The presence of alopecia of any grade and peripheral neuropathy ≤ grade 2 without pain is allowed. 7. Previous allogeneic stem cell transplantation with active graft-versus-host-disease, or treatment with immunosuppressive therapy in the 2 months prior to study entry. 8. Daily requirement for corticosteroids \>10 mg prednisone daily (or equivalent); inhaled corticosteroids are permitted. 9. Patient is known to be human immunodeficiency virus positive, or have chronic or active hepatitis B (core- or surface antigen-positive) or active hepatitis C infection. 10. Clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association \[NYHA\] Class 3 or 4, congestive heart failure, uncontrolled or unstable angina, history of myocardial infarction or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication) 11. Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study. 12. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements. 13. History of erythema multiforme or severe hypersensitivity to prior Immunomodulatory Drugs (IMiDs) such as thalidomide and lenalidomide. 14. The patient is receiving medications that are strong inhibitors of CYP1A2. Patients should have discontinued strong CYP1A2 inhibitors (e.g., ciprofloxacin and fluvoxamine) at least 5 half-lives before beginning study drug. 15. The patient continues to smoke cigarettes, which can induce CYP1A2. 16. Inability to tolerate thromboprophylaxis. 17. Pregnant or breast feeding.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Dose Level 1: single-agent SL-401 7 µg/kg/day on Days 1-5 during the initial 28-day run-in cycle followed by a combination of SL-401/pomalidomide/dexamethasone (pom/dex) if there was no dose-limiting toxicity during the run-in cycle
intervention Names
Drug: SL-401 7 µg/kg/day
label
Phase 1, SL-401 7 µg/kg/day
type
EXPERIMENTAL
description
Dose Level 2: SL-401 9 µg/kg/day in combination with pom/dex
intervention Names
Drug: SL-401 9 µg/kg/day
label
Phase 1, SL-401 9 µg/kg/day
type
EXPERIMENTAL

interventions

arm Group Labels
Phase 1, SL-401 7 µg/kg/day
description
SL-401 7 µg/kg/day in combination with pom/dex
name
SL-401 7 µg/kg/day
other Names
tagraxofusp-erzs
type
DRUG
arm Group Labels
Phase 1, SL-401 9 µg/kg/day
description
SL-401 9 µg/kg/day in combination with pom/dex
name
SL-401 9 µg/kg/day
other Names
tagraxofusp-erzs
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 9
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
To evaluate the safety of single agent SL-401 in an initial run-in cycle in patients with multiple myeloma
measure
Number of Patients With Dose-limiting Toxicities and Treatment-emergent Adverse Events
time Frame
For a 28-day cycle, Cycle 1
description
To evaluate the safety of single agent SL-401 in an initial run-in cycle in patients with multiple myeloma
measure
Number of Patients With Treatment-related Adverse Events
time Frame
Up to 12 months
description
To evaluate the safety of single agent SL-401 in an initial run-in cycle in patients with multiple myeloma (MM)
measure
Treatment-Emergent Adverse Events Leading to Discontinuation of Study Drug
time Frame
Up to 12 Months

secondary Outcomes

description
Overall response rate is defined as complete response + very good partial response + partial response and clinical benefit rate (CR + VGPR + PR + minimal response \[MR\]) based on International Myeloma Working Group-defined response criteria and the duration of response (DOR) in relapsed refractory multiple myeloma (RRMM) patients.
measure
Overall Response Rate
time Frame
Up to 12 Months
description
Per International Myeloma Working Group Response Criteria, progression/progressive disease is defined as increase of \>25% from lowest response value in any 1 of the following: serum M-component (the absolute increase must be \>0.5 g/dL)4 and/or urine M-component (the absolute increase must be \>200 mg/24 h) and/or; only in patients without measurable serum and urine M-protein, the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL; only in patients without measurable serum and urine M-protein and without measurable disease by FLC levels; bone marrow plasma cell percentage (absolute % must be ≥10%); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder.
measure
Progression-free Survival
time Frame
Up to 12 Months

Full study description

brief Summary: A Phase 1/2, Open Label Study of SL-401 in Combination with Pomalidomide and Dexamethasone In Relapsed and Refractory Multiple Myeloma
detailed Description: This study is a phase 1/2 multicenter, open-label study of SL-401 (tagraxofusp-erzs) in combination with standard doses of pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (MM). The study will be conducted in 2 phases: Phase 1 is the dose-escalation phase to determine the maximum tested dose (MTD) of SL-401 in combination with standard doses of pomalidomide and dexamethasone. In Phase 1, each evaluated SL-401 dose level will incorporate an initial "Run-in Cycle" (i.e. cycle 1) of single agent SL-401 in at least 3 patients; following the Run-in Cycle, patients who have not experienced a dose-limiting toxicity (DLT) will receive combination SL-401/pomalidomide and dexamethasone in cycles 2 and beyond. All patients in Phase 2 will receive 1 cycle of SL-401 monotherapy in cycle 1, followed by combination of SL-401/pomalidomide/dexamethasone in cycle 2 and beyond. The dose of SL-401 will be the MTD of SL-401 or MTD given in combination with pomalidomide/dexamethasone determined during Phase 1.

Source references

references

citation
Agarwal A, Ghobrial IM. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease. Clin Cancer Res. 2013 Mar 1;19(5):985-94. doi: 10.1158/1078-0432.CCR-12-2922. Epub 2012 Dec 5.
pmid
23224402
type
BACKGROUND
citation
Aldinucci D, Olivo K, Lorenzon D, Poletto D, Gloghini A, Carbone A, Pinto A. The role of interleukin-3 in classical Hodgkin's disease. Leuk Lymphoma. 2005 Mar;46(3):303-11. doi: 10.1080/10428190400013712.
pmid
15621820
type
BACKGROUND
citation
Aldinucci D, Poletto D, Gloghini A, Nanni P, Degan M, Perin T, Ceolin P, Rossi FM, Gattei V, Carbone A, Pinto A. Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg cells. Am J Pathol. 2002 Feb;160(2):585-96. doi: 10.1016/S0002-9440(10)64878-X.
pmid
11839579
type
BACKGROUND
citation
Alexander RL, Kucera GL, Klein B, Frankel AE. In vitro interleukin-3 binding to leukemia cells predicts cytotoxicity of a diphtheria toxin/IL-3 fusion protein. Bioconjug Chem. 2000 Jul-Aug;11(4):564-8. doi: 10.1021/bc000009q.
pmid
10898579
type
BACKGROUND
citation
American Cancer Society. Cancer Facts and Figures 2013. Available from: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc- 036845.pdf.
type
BACKGROUND
citation
Angelot-Delettre F, Frankel AE, Liu SE et al. The IL-3Rα-Targeted Drug SL-401 Selectively kills Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Cells. ASH 2011, Poster #2588.
type
BACKGROUND
citation
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756-60. doi: 10.1038/nature05236. Epub 2006 Oct 18.
pmid
17051156
type
BACKGROUND
citation
Black JH, McCubrey JA, Willingham MC, Ramage J, Hogge DE, Frankel AE. Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice. Leukemia. 2003 Jan;17(1):155-9. doi: 10.1038/sj.leu.2402744.
pmid
12529673
type
BACKGROUND
citation
Chauhan D, Ray A, Brooks C et al. A Novel Agent SL-401 Targeting Interleukin-3 (IL-3)- Receptor Blocks Plasmacytoid Dendritic Cell (pDC)-induced Myeloma Cell Growth and Overcomes Drug Resistance. J Clin Oncol 2013; 31;(suppl; abstr 8582).
type
BACKGROUND
citation
Chauhan D, Singh AV, Brahmandam M, Carrasco R, Bandi M, Hideshima T, Bianchi G, Podar K, Tai YT, Mitsiades C, Raje N, Jaye DL, Kumar SK, Richardson P, Munshi N, Anderson KC. Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell. 2009 Oct 6;16(4):309-23. doi: 10.1016/j.ccr.2009.08.019.
pmid
19800576
type
BACKGROUND
citation
Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto K, Libermann TA, Anderson KC. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood. 1996 Feb 1;87(3):1104-12.
pmid
8562936
type
BACKGROUND
citation
Deng Q, Barbieri JT. Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. Annu Rev Microbiol. 2008;62:271-88. doi: 10.1146/annurev.micro.62.081307.162848.
pmid
18785839
type
BACKGROUND

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice