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

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ClinicalTrials.gov Identifier: NCT02661022
Recruitment Status : Recruiting
First Posted : January 21, 2016
Last Update Posted : March 1, 2019
Sponsor:
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: SL-401/ Pomalidomide/ Dexamethasone Phase 1 Phase 2

Detailed Description:

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

This study is a Phase 1/2 multi center, open label study of SL-401 in combination with standard doses of Pomalidomide and Dexamethasone. The study will be conducted in 2 Phases: Phase 1 is the dose escalation Phase to determine the MTD or maximum tested dose 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 DLT will receive combination SL-401/Pomalidomide and Dexamethasone in cycles 2 and beyond. All patients in Phase 2 will initiate therapy with the combination of SL-401/Pomalidomide and Dexamethasone at the maximum tested dose established in Phase 1 in the same manner (i.e. SL-401 alone in cycle 1 followed by combination of SL-401 and Pomalidomide and Dexamethasone in cycles 2 and beyond).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open Label Study of SL-401 in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : January 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: SL-401/Pomalidomide/ Dexamethasone
SL-401 in combination with Pomalidomide and Dexamethasone
Drug: SL-401/ Pomalidomide/ Dexamethasone
Other Name: tagraxofusp-erzs




Primary Outcome Measures :
  1. The percentage of patients with treatment-related and treatment-emergent adverse events [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. SL-401 plasma concentration at multiple time points [ Time Frame: Up to 12 Months ]
  2. SL-401 maximum plasma concentration [ Time Frame: Up to 12 Months ]
  3. Overall response rate [ Time Frame: Up to 12 Months ]
  4. Progression free survival [ Time Frame: Up to 12 Months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02661022


Contacts
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Contact: Shay Shemesh 718-509-3742 Trials@stemline.com

Locations
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United States, California
City of Hope Active, not recruiting
Duarte, California, United States, 91010
United States, Massachusetts
Dana Farber Cancer Institue Recruiting
Boston, Massachusetts, United States, 02215
Contact: Paul Richardson, MD    617-632-2127    Paul_Richardson@dfci.harvard.edu   
United States, Oregon
Oregon Health & Science University Active, not recruiting
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Stemline Therapeutics, Inc.

Publications:
American Cancer Society. Cancer Facts and Figures 2013. Available from: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc- 036845.pdf.
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.
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).
Frolova O, Frankel AE, Korchin B et al. IL3R-Directed Agents, SL-401 and SL-501, Inhibit the Growth of Leukemia Stem cells in CML. Blood (ASH Meeting Abstracts) 2010 116: Abstract 3403.
National Cancer Institute-Common Terminology Criteria: Version 4.03 reference, accessible through the NCI website at http://ctep.info.nih.gov/reporting/ctc.html.
Pomalidomide Perscribing Information. POMPI.001/MG.001 02/13. Reference ID: 325852

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Responsible Party: Stemline Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02661022     History of Changes
Other Study ID Numbers: STML-401-0414
First Posted: January 21, 2016    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents