INCB053914 and Pomalidomide With Dexamethasone for Relapsed and/or Refractory Multiple Myeloma

NCT04355039 | Withdrawn Phase 1 DMC

• 1 other identifier: IIT-Dhakal-INCB053914
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, single-center, open-label phase Ib study aimed at determining a recommended phase II dose of INCB053914 and pomalidomide with dexamethasone. The trial will follow a 3 + 3 phase I dose-escalation design.

Conditions

Refractory Multiple Myeloma; Relapse Multiple Myeloma

Keywords

Multiple Myeloma; Refractory Multiple Myeloma; Relapse Multiple Myeloma; INCB053914; pan-PIM Kinase Inhibitor

Outcome Measures

Primary Outcomes (1)

• The number of subjects with dose-limiting toxicities.

  The safety of INCB053914 with pomalidomide and dexamethasone in participants with relapsed and/or refractory multiple myeloma.

  28 days

Secondary Outcomes (8)

• The recommended phase II dose of INCB053914.

  28 days

• Progression-free survival.

  2 Years

• Overall survival.

  2 Years

• Duration of response.

  2 Years

• Efficacy of bone protective effect of INCB053914 in combination with pomalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma.

  7 months

Study Arms (3)

Pomalidomide, Dexamethasone & INCB053914 50 mg twice daily

EXPERIMENTAL

INCB053914 will have a dose escalation in a 3 + 3 design.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 50 mg bis in die (BID)

Pomalidomide, Dexamethasone & INCB053914 65 mg twice daily

EXPERIMENTAL

INCB053914 will have a dose escalation in a 3 + 3 design.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 65 mg BID

Pomalidomide, Dexamethasone & INCB053914 80 mg twice daily

EXPERIMENTAL

INCB053914 will have a dose escalation in a 3 + 3 design.

Drug: Pomalidomide; Drug: Dexamethasone; Drug: INCB053914 80 mg BID

Interventions

Pomalidomide DRUG

4 mg Days 1-21

Also known as: Pomalyst

Pomalidomide, Dexamethasone & INCB053914 50 mg twice daily; Pomalidomide, Dexamethasone & INCB053914 65 mg twice daily; Pomalidomide, Dexamethasone & INCB053914 80 mg twice daily

Dexamethasone DRUG

40 mg Days 1, 8, 15 and 22

Also known as: Ozurdex

Pomalidomide, Dexamethasone & INCB053914 50 mg twice daily; Pomalidomide, Dexamethasone & INCB053914 65 mg twice daily; Pomalidomide, Dexamethasone & INCB053914 80 mg twice daily

INCB053914 50 mg bis in die (BID) DRUG

Dose level 0: 50 mg BID

Also known as: pan-PIM Kinase Inhibitor

Pomalidomide, Dexamethasone & INCB053914 50 mg twice daily

INCB053914 65 mg BID DRUG

Dose level 1: 65 mg BID

Also known as: pan-PIM Kinase Inhibitor

Pomalidomide, Dexamethasone & INCB053914 65 mg twice daily

INCB053914 80 mg BID DRUG

Dose level 2: 80 mg BID

Also known as: pan-PIM Kinase Inhibitor

Pomalidomide, Dexamethasone & INCB053914 80 mg twice daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Patient should have received ≥2 lines of therapy including at least two consecutive cycles of lenalidomide and a proteasome inhibitor alone or in combination and should be relapsed and/or refractory to lenalidomide and a proteasome inhibitor.
• Measurable disease as defined (at least one of the following):
• Serum M-protein level ≥0.5 g/dl or urine M-protein level ≥200 mg/24 hours. OR
• Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
• Non-secretory multiple myeloma (MM) with bidimensionally measurable plasmacytoma.
• Male or female subjects ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Female subjects must meet one of the following:
• Postmenopausal for at least one year before enrollment, OR
• Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
• If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agrees to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 21days after the last dose of study agent, OR o Agrees to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.)
• Male subjects, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
• Practice effective barrier contraception during the entire study period and through 90 calendar days after the last dose of study agent, OR
• o Agrees to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.)

You may not qualify if:

• Prior use of PIM kinase inhibitors.
• Prior pomalidomide refractory patients (last prior therapy was pomalidomide-containing regimen and/or patients within three months of pomalidomide dose).
• Diagnosed or treated for malignancy other than multiple myeloma, except:
• Malignancy treated with curative intent and with no known active disease present for ≥2 years before enrollment.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ (e.g., cervical, breast) with no evidence of disease.
• Exhibiting clinical signs of meningeal or central nervous system involvement by multiple myeloma.
• Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C.
• Concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study. Specifically, any potential subject who is unsuitable for autologous stem cell transplant (ASCT) would be excluded from the study.
• Clinically significant cardiac disease, including:
• Myocardial infarction within six months before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] Version 5 grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec.
• Any of the following laboratory test results during the screening phase:
• Absolute neutrophil count \<1.0 × 109/L; no granulocyte-colony stimulating factor (G-CSF) treatment in the past seven days are allowed.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; Dexamethasone; Calcium Dobesilate; BID protein, human

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Binod Dhakal, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 21, 2020
• Study Start: July 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2024
• Last Updated: August 19, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share