A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Oprozomib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Withdrawn

• Conditions: Kahler's disease; plasma cell myeloma; Relapsed or Refractory Multiple Myeloma; 10018865

• Registration Number: NL-OMON46679
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 3

Inclusion Criteria

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Age >= 18 years old at the time of signing the informed consent
• Subject must have a pathologically documented, definitively diagnosed, multiple myeloma relapse, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide
• Subject must be willing and able to undergo bone marrow aspirate per protocol

• Measurable disease (assessed within 28 days prior to day 1), as indicated by one or more of the following:
Serum M-protein >= 0.5 g/dL
Urine M-protein >= 200 mg/24 hours
In subjects without detectable serum or urine M-protein: serum Free Light
Chain (sFLC) >= 10 mg/dL (>= 100 mg/L) and an abnormal sFLC ratio
• Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
• Hematological function, as follows, without transfusion support:
Absolute neutrophil count >= 1.0 X 109/L
Platelet count >= 75 X 109/L (in patients with < 50% of bone marrow nucleated cells were plasma cells) or >= 50 X 109/L (in patients with >= 50% of bone
marrow nucleated cells were plasma cells) without transfusion or growth factor support
Hemoglobin > 8 g/dL (> 80 g/L) Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however most recent RBC transfusion must be
7 days prior to obtaining screening hemoglobin

• Coagulation function as follows: PT/INR and PTT < 1.5 x Institutional Upper Limit of Normal (ULN)
• Renal function as follows: estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation (MDRD) > 30 mL/min/1.73 m2
• Hepatic function, as follows: AST and ALT < 3 x ULN, Total bilirubin < 1.5 x ULN (except subjects with Gilbert*s syndrome)

Exclusion Criteria

• Currently receiving treatment in another investigational device or drug study, or less than 28 days or 5 half-lives, whichever is shorter, since ending treatment on another investigational device ordrug study(s)
• Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following:
received the transplant within 6 months prior to study day 1
received immunosuppressive therapy within the last 3 months prior to study day 1
having signs or symptoms of acute or chronic graft-versus-host disease
• Autologous stem cell transplant < 90 days prior to study day 1
• Multiple myeloma with IgM subtype
• POEM syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (> 2.0 X109/L circulating plasma cells by standard differential)
• Waldenstrom*s macroglobulinemia
• Amyloidosis
• Requirement for plasmapheresis during the screening period
• Dexamethasone at cumulative doses of greater than 160 mg or equivalent within 21 days prior to study day 1 is not allowed. Use of topical or inhaled steroids is Acceptable
• History of other malignancy, except:
Malignancy treated with curative intent and with no known active disease present for >= 1 year before study day 1 and felt to be at low risk for recurrence by the treating physician
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated cervical carcinoma in situ without evidence of disease
Adequately treated breast ductal carcinoma in situ without evidence of disease
Prostatic intraepithelial neoplasia without evidence of prostate cancer
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ

• Evidence of a bleeding diathesis
• Current use of therapeutic doses of anticoagulation unless agreed upon by the investigator and the Amgen Medical Monitor. Please note: thromboprophylaxis is recommended with pomalidomide treatment
• Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II).
• Infection requiring anti-infective treatments (oral or intravenous) within 2 weeks of study day 1.
• Hepatitis B and C based on the following results:
Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B
Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C
• History of clinically significant GI hemorrhage (Grade >= 2) in the 6 months prior to study day 1, unless agreed upon by the investigator and the Amgen Medical Monitor
• Known positive results for Human Immunodeficiency Virus (HIV)
• Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade 1, or to levels dictated in the eligibility criteria with the exception of Grade 2 peripheral neuropathy, alopecia or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 4 weeks may be all

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* Determine the MTD for each formulation of oprozomib in combination with<br /><br>pomalidomide and dexamethasone as the dose that has the highest posterior<br /><br>probability of having a dose limiting toxicity (DLT) rate within the target<br /><br>toxicity interval (15% to 25%), while the posterior probability of<br /><br>excessive/unacceptable toxicity (> 25% to 100%) is < 40%<br /><br>* Incidence of treatment-related, treatment-emergent adverse events and changes<br /><br>in laboratory test results</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* PK parameters of oprozomib including, but not limited to, maximum observed<br /><br>concentration (Cmax), time to Cmax (tmax), and the area under the<br /><br>concentration-time curve from time 0 to the time of the last quantifiable<br /><br>concentration (AUClast)<br /><br>* Overall response and best overall response according to the IMWG uniform<br /><br>response criteria, progression free survival (PFS), and duration of response<br /><br>(DOR)Nature and extent of the burden and risks associated with participation,<br /><br>benefit and group relatedness (if applicable): </p><br>