Pomalidomide for Lenalidomide for Relapsed or Refractory Multiple Myeloma Patients

NCT02188368 | Terminated Phase 2 DMC

• 1 other identifier: PO-CL-MM-PI-003854
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of pomalidomide given as part of a combination therapy that include more than just steroids to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM). Pomalidomide (alone or in combination with dexamethasone) has been approved by the United States Food and Drug Administration (FDA) for the treatment of MM patients who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of their last therapy. However, the use of pomalidomide in combination with other drugs used to treat MM, such as chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere with the development of small blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. The testing done with pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM both on its own and in combination with dexamethasone. Using another drug class, namely proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with another in an established anti-myeloma treatment regimen can frequently overcome resistance regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the toxicity profile of the new combinations closely resembled that of the proteasome inhibitor administered as a single agent. Based on this experience, we hypothesize that the replacement of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory MM patient population.

Conditions

Multiple Myeloma

Keywords

Pomalidomide; Lenalidomide refractory; multiple myeloma

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD)

  MTD will be determined for any ≥ three-drug combinations other than: bortezomib + steroids + lenalidomide; carfilzomib + steroids + lenalidomide; clarithromycin + steroids + lenalidomide; cyclophosphamide + steroids + lenalidomide pegylated liposomal doxorubicin (PLD) + lenalidomide with or without steroids

  Cycles 1-3 for selected regimens (up to 3 months)

• Number of subjects with adverse events

  Adverse events will be graded via the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.

  up to 36 months

• Overall Response Rate

  Overall response rate (ORR): complete response (CR)+ very good partial response (VGPR) + partial response (PR)

  up to 36 months

• Clinical Benefit Rate (CBR)

  CBR=ORR + minor response (MR)

  up to 36 months

Secondary Outcomes (5)

• Time to Progression

  time from initiation of therapy to progressive disease (assessed at least over 36 months)

• Progression-free survival (PFS)

  time from initiation of therapy to progressive disease or death from any cause, whichever comes first (assessed at least over 36 months)

• Time to first response (TTP)

  time from initiation of therapy to the first evidence of a confirmed response (up to 36 months)

• Duration of response (DOR)

  time from the first response (> PR) to progressive disease (assessed at least over 36 months)

• Overall survival (OS)

  time from initiation of therapy to death from any cause or last follow-up visit (assessed at least over 36 months).

Study Arms (3)

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)

EXPERIMENTAL

POM 4 mg PO days 1-21 Steroids at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject). BTZ (bortezomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject). CFZ (carfilzomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject). CLA (clarithromycin) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject). CY (cyclophosphamide) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).

Drug: POM; Drug: Steroids; Drug: CFZ; Drug: BTZ; Drug: CLA; Drug: CY

B: POM 3mg+PLD with or without steroids

EXPERIMENTAL

POM 3 mg PO days 1-21 Steroids (if the patient had received them) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject). PLD at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).

Drug: POM; Drug: Steroids; Drug: PLD

C: POM MTD + other drugs

EXPERIMENTAL

Phase 1: POM at escalating doses of 2 mg (Cycle 1), 3 mg (Cycle 2) or 4 mg (Cycle 3+) All other agents at the same dose and on the same days as the patients were receiving them in the lenalidomide-containing regimen they had failed Phase 2: POM at the MTD All other agents, at the same dose and on the same days as phase 1

Drug: POM

Interventions

POM DRUG

Also known as: Pomalidomide, Pomalyst, Actimid, CC-4047

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA); B: POM 3mg+PLD with or without steroids; C: POM MTD + other drugs

Steroids DRUG

Also known as: Dexamethasone, prednisone, methyprednisolone

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA); B: POM 3mg+PLD with or without steroids

PLD DRUG

Also known as: Pegylated liposomal doxirrubicin

B: POM 3mg+PLD with or without steroids

CFZ DRUG

Also known as: Carfilzomib, Kyprolis

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)

BTZ DRUG

Also known as: Bortezomib, Velcade

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)

CLA DRUG

Also known as: Clarithromycin

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)

CY DRUG

Also known as: Cyclophosphamide

A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)

Eligibility Criteria

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

You may qualify if:

• Has a diagnosis of MM based on standard criteria as follows:
• Major criteria:
• plasmacytomas on tissue biopsy
• bone marrow plasmacytosis (greater than 30% plasma cells)
• monoclonal immunoglobulin (Ig) spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain excretion greater than 1 g/day on 24-hour urine protein electrophoresis
• Minor criteria:
• bone marrow plasmacytosis (10% to 30% plasma cells)
• monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
• lytic bone lesions
• normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL
• Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
• any 2 of the major criteria
• major criterion 1 plus minor criterion 2, 3, or 4
• major criterion 3 plus minor criterion 1 or 3
• minor criteria 1, 2, and 3, or 1, 2, and 4

You may not qualify if:

• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes (POEMS) syndrome
• Plasma cell leukemia
• Primary amyloidosis
• Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
• Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Received the following prior therapy:
• Pomalidomide
• Lenalidomide alone or in combination with steroids in their last treatment regimen. Interim therapy not containing lenalidomide between their last lenalidomide-containing regimen and the start of the trial.
• A melphalan-containing regimen as the immediate prior line of treatment
• Chemotherapy within 3 weeks of study drugs (6 weeks for nitrosoureas)
• Corticosteroids (\>10 mg /daily prednisone or equivalent) within 3 weeks of study drugs
• Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before study drugs
• Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
• Use of any other experimental drug or therapy within 28 days of study drugs
• Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide.

Sponsors & Collaborators

• Oncotherapeutics: lead
• Celgene Corporation: collaborator

Study Sites (12)

California Cancer Associates for Research & Excellence (cCARE)

Encinitas, California, 92024, United States

Location

Compassionate Care Research Group

Fountain Valley, California, 92708, United States

Location

Comprehensive Cancer Center at Desert Regional Medical Center

Palm Springs, California, 92262, United States

Location

Inland Hematology Oncology Medical Group, Inc

San Bernardino, California, 92404, United States

Location

Wellness Oncology and Hematology

West Hills, California, 91307, United States

Location

James R. Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

VA Sierra Nevada

Reno, Nevada, 89502, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Wellmont Medical Associates Oncology and Hematology

Kingsport, Tennessee, 37660, United States

Location

Vista Oncology

Olympia, Washington, 98502, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; Steroids; Dexamethasone; Prednisone; 1-dodecylpyridoxal; carfilzomib; Bortezomib; Clarithromycin; Cyclophosphamide

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)

Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids, Fluorinated; Pregnadienediols; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• James R Berenson, MD

  James R. Berenson MD, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 11, 2014
• Study Start: July 7, 2014
• Primary Completion: October 23, 2020
• Study Completion: October 23, 2020
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

US (12)