Open Label Study With Imetelstat to Determine Effect of Imetelstat in Patients w/ Previously Treated Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Geron Corporation
ClinicalTrials.gov Identifier:
NCT01242930
First received: November 16, 2010
Last updated: April 13, 2016
Last verified: April 2016
  Purpose
This is an open label Phase II study to determine the rate of improvement in response of patients with previously treated multiple myeloma to imetelstat alone or in combination with lenalidomide maintenance therapy. This study will include multiple myeloma patients who either have achieved disease stabilization or who have achieved at least a partial response (PR) but failed to achieve a complete response (CR) after cytoreductive therapy for multiple myeloma; ie, have detectable but non-progressing disease and will most likely relapse.

Condition Intervention Phase
Multiple Myeloma
Drug: Imetelstat (7.5 mg/kg)
Drug: lenalidomide standard of care
Drug: Imetelstat (9.4 mg/kg)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial to Determine the Effect of Imetelstat (GRN163L) on Patients With Previously Treated Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Geron Corporation:

Primary Outcome Measures:
  • Rate of Improvement in Response [ Time Frame: From time of first dose (Cycle 1 day 1) through end of study period (12 mos. after last participant is enrolled) ] [ Designated as safety issue: No ]
    To determine the rate of improvement in response in patients with previously treated multiple myeloma following treatment with imetelstat alone or in combination wtih lenalidomide maintenance therapy. Response will be assessed using the International Uniform Response Criteria for Multiple Myeloma (IURCMM).


Secondary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: From time of first dose (Cycle 1 day 1) through end of study (12 mos. after last participant is enrolled) ] [ Designated as safety issue: No ]
    As assessed from Cycle 1 Day 1 to first evidence of PD as defined by IURCMM, or death, whichever occurs first.

  • Safety and Tolerability [ Time Frame: From time of first dose (Cycle 1 day 1) through end of study (12 mos. after last participant is enrolled) ] [ Designated as safety issue: Yes ]

    The safety and tolerability of imetelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.

    Patients who develop Grade 3 or 4 cytopenias (other than lyphophenia and/or leukopenia alon) will receive addiontal safety monitoring for reversibility.



Enrollment: 13
Study Start Date: November 2010
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imetelstat (7.5 mg/kg)
Imetelstat (7.5 mg/kg) with or without lenalidomide standard of care
Drug: Imetelstat (7.5 mg/kg)
Imetelstat 7.5 mg/kg as a 2-hour intravenous infusion (± 10 minutes) on Days 1 and 8 of a 28-day cycle; the Day 8 dose will be omitted in patients with a prior history of bone marrow or stem cell transplant.
Other Name: GRN163L
Drug: lenalidomide standard of care
Patients who are receiving lenalidomide as maintenance therapy upon enrollment as part of their treatment regimen may remain on this therapy during trial participation, provided that they have received this treatment for a minimum of 3 months and demonstrate evidence of stabilization of their response.
Other Name: Revlimid
Experimental: Imetelstat (9.4 mg/kg)
Imetelstat (9.4 mg/kg) with or without lenalidomide standard of care
Drug: lenalidomide standard of care
Patients who are receiving lenalidomide as maintenance therapy upon enrollment as part of their treatment regimen may remain on this therapy during trial participation, provided that they have received this treatment for a minimum of 3 months and demonstrate evidence of stabilization of their response.
Other Name: Revlimid
Drug: Imetelstat (9.4 mg/kg)
Imetelstat 9.4 mg/kg as a 2-hour intravenous infusion (± 10 minutes) on Days 1 and 8 of a 28-day cycle; the Day 8 dose will be omitted in patients with a prior history of bone marrow or stem cell transplant.
Other Name: GRN163L

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Willing and able to sign an informed consent Male or female, 18 years or older Confirmed diagnosis of multiple myeloma (secretory disease) by International Myeloma Working Group Diagnostic Criteria

Patients must meet one of the following criteria:

o Previously treated patients with multiple myeloma who achieved at least stable disease but who have failed to achieve a complete response (CR) after a minimum of one cytoreductive therapy for multiple myeloma and have detectable but non-progressing disease. Patients must have received at least one proteasome inhibitor (eg, bortezomib) or one immunomodulatory agent (eg, thalidomide or lenalidomide) or both.

Patients receiving lenalidomide as maintenance therapy may continue to receive this therapy provided that the patient has been on this maintenance therapy for a minimum of 3 months and has evidence of disease stabilization.

Disease stabilization will be defined as an M protein that varies ≤ 25% over the three measurements or remains under 0.5 g/dL whichever is smaller.

ECOG performance status 0-2 Life expectancy ≥ 3 months

Laboratory criteria (within 14 days of first study drug administration):

  • ANC ≥ 1000/μL
  • Platelet count ≥ 50 x 103/μL (without transfusion support within 2 weeks prior to first study drug administration)
  • Hemoglobin ≥ 8.0 g/dL
  • Serum creatinine ≤ 3 x the upper limit of normal (ULN)
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x the upper limit of normal (ULN), unless due to disease.

Must have fully recovered from any previous cancer treatments and/or major surgery.

Women of childbearing potential must have a negative serum pregnancy test and agree to use effective birth control (two reliable forms of contraception) during and for at least 12 weeks after the last treatment.

Males must agree to use effective birth control for themselves or their partner during and for 12 weeks after the last treatment with imetelstat. For those patients receiving lenolidomide, males must use latex condom during sexual contact with women of childbearing potential even if they have undergone a successful vasectomy.

Exclusion Criteria:

Women who are pregnant or breast feeding Prior radioimmunotherapy. Known intracranial disease or epidural disease. Patients with lytic lesions of the cranium or spine secondary to myeloma are eligible to enroll.

Clinically significant cardiovascular disease or condition including:

  • Congestive heart failure (CHF) requiring therapy
  • Need for antiarrhythmic therapy for a ventricular arrhythmia
  • Severe conduction disturbance
  • Angina pectoris requiring therapy
  • Uncontrolled hypertension per the Investigator's discretion
  • New York Heart Association Class II, III, or IV cardiovascular disease Active or chronically recurrent bleeding (eg, active peptic ulcer disease) Clinically relevant active infection. Serious co-morbid medical conditions, including cirrhosis and chronic obstructive or chronic restrictive pulmonary disease.

Symptomatic hyperviscosity syndrome. Any other cancer therapy including chemotherapy, monoclonal antibody, signal transduction inhibitor, immunotherapy, glucocorticoid (except topical or as premedication), thalidomide within 3 weeks prior to first study drug administration.

Investigational therapy within 4 weeks prior to first study drug administration.

Major surgery within 4 weeks prior to first study drug administration (central line placement is allowed) Anti-platelet therapy within 2 weeks prior to first study drug administration, other than low dose aspirin prophylaxis therapy.

Full dose anticoagulation. Prophylactic low dose administration for management of IV access devices is allowed.

Known positive serology for human immunodeficiency virus (HIV. Any other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for this study

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01242930

Locations
United States, Maryland
University of Maryland Medical Center - M & S Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
Sidney Kimmel Cancer Center Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Geron Corporation
Investigators
Study Director: Ted Shih, PharmD Geron Corporation
Principal Investigator: Carol Ann Huff, M.D. Sidney Kimmel Cancer Center at Johns Hopkins Hospital
  More Information

Responsible Party: Geron Corporation
ClinicalTrials.gov Identifier: NCT01242930     History of Changes
Other Study ID Numbers: CP14B013 
Study First Received: November 16, 2010
Last Updated: April 13, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Geron Corporation:
imetelstat
imetelstat sodium
GRN163L
telomerase inhibitor
telomerase inhibition
multiple myeloma
myeloma
myeloma progenitor cells

Additional relevant MeSH terms:
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
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2016