Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Murali Janakiram, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01899326
First received: July 11, 2013
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

This pilot clinical trial studies how well desipramine hydrochloride and filgrastim works for stem cell mobilization in patients with multiple myeloma undergoing stem cell transplant. Giving colony-stimulating factors, such as filgrastim, and other drugs, such as desipramine hydrochloride, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored.


Condition Intervention
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: desipramine hydrochloride
Biological: filgrastim
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Clinical Study of GCSF in Combination With Desipramine for Autologous Stem Cell Mobilization in Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Success rate of stem cell mobilization (SCM) using filgrastim and desipramine to collect > 5 x 10^6 cluster of differentiation (CD)34/kg in patients with multiple myeloma (MM) who are first time mobilizers or unexposed to alkylating agents [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables. The success rates observed in first-time mobilizers, along with corresponding 95% binomial confidence intervals, will be estimated.

  • Success rate of SCM using filgrastim and desipramine to achieve a total collection of > 5 x 10^6 CD34/kg in patients with MM who failed prior mobilization or were exposed to alkylator therapy or are predicted to be difficult to mobilize [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables. The success rates observed in predicted difficult mobilizers, along with corresponding 95% binomial confidence intervals, will be estimated.


Secondary Outcome Measures:
  • Average number of days of apheresis required to collect > 5 x 10^6 CD34+/kg [ Time Frame: Up to 1 week after completion of study treatment ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables.

  • Incidence of adverse events graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 1 week after completion of study treatment ] [ Designated as safety issue: Yes ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables.

  • Time to neutrophil engraftment: first of three consecutive days with absolute neutrophil count (ANC) > 500/ul or first day with ANC > 1000/ul in the absence of growth factor support [ Time Frame: Up to 1 week after completion of study treatment ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables.

  • Time to platelet engraftment: first of three days of platelets > 20,000/ul without transfusion [ Time Frame: Up to 1 week after completion of study treatment ] [ Designated as safety issue: No ]
    Standard descriptive statistics will be used to summarize the data, including means, medians, standard deviations and ranges for continuous variables, and frequencies for categorical variables.


Estimated Enrollment: 40
Study Start Date: December 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (desipramine, filgrastim)
Patients receive desipramine hydrochloride PO daily on days -3 to +4 and filgrastim PO BID on days 1-4. Stem cell collection begins on day 6.
Drug: desipramine hydrochloride
Given PO
Other Names:
  • Norpramin
  • Pertofrane
Biological: filgrastim
Given PO
Other Names:
  • G-CSF
  • Neupogen
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To study efficacy, safety, harvest kinetics and engraftment kinetics of patients undergoing autologous stem cell mobilization, mobilized with a combination of granulocyte colony-stimulating factor (GCSF) (filgrastim) with desipramine (desipramine hydrochloride) (G+D).

II. To analyze polymorphisms of adrenergic receptor beta 2 (ADRB2) and adrenergic receptor beta 3 (ADRB3) genes that correlate with mobilization efficiency.

OUTLINE:

Patients receive desipramine hydrochloride orally (PO) daily on days -3 to +4 and filgrastim PO twice daily (BID) on days 1-4. Stem cell collection begins on day 6.

After completion of study treatment, patients are followed up 1 week after completion of stem cell collection.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients eligible for autologous stem cell transplant for multiple myeloma; planned use of filgrastim (GCSF) for stem cell mobilization
  • Ability to give informed consent
  • Glomerular filtration rate (GFR) > 30 ml/minute
  • Liver function tests < 2.5 x upper limit of normal (ULN)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or less
  • Based on prior therapy patients will be classified into two categories:

    • Initial mobilizers with no exposure to alkylators
    • Remobilizers or with prior exposure to alkylators or with greater than 5 cycles of lenalidomide therapy prior to mobilization

Exclusion Criteria:

  • Use of a monoamine oxidase inhibitor (MAO-I) during or within 2 weeks of desipramine therapy
  • Concomitant therapy with any drugs shown to have major interactions with desipramine
  • Concurrent use of drugs that are contraindicated with desipramine
  • Myocardial infarction in preceding 4 weeks; history of uncontrolled cardiac arrhythmias or family history of sudden cardiac death; baseline corrected QT (QTc) > 460 msec
  • Active alcohol abuse
  • Bipolar disorder
  • Untreated active major depression
  • History of seizures in the past 3 years
  • Pregnancy and lactation; refusal to use adequate contraception
  • Uncontrolled thyroid disease
  • GCSF or pegfilgrastim use within 14 days prior to enrollment
  • Bortezomib, Revlimid or thalidomide use within 7 days of enrollment
  • Patients with sickle cell disease
  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: NCT01899326

Locations
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Murali Janakiram    718-920-4826    MJANAKIR@montefiore.org   
Principal Investigator: Murali Janakiram         
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Principal Investigator: Murali Janakiram Albert Einstein College of Medicine of Yeshiva University
  More Information

No publications provided

Responsible Party: Murali Janakiram, Principal Investigator, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT01899326     History of Changes
Other Study ID Numbers: 2012-230, NCI-2013-01212, 11-010, 2012-230, P30CA013330
Study First Received: July 11, 2013
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Desipramine
Lenograstim
Adjuvants, Immunologic
Adrenergic Agents
Adrenergic Uptake Inhibitors
Antidepressive Agents
Antidepressive Agents, Tricyclic
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs

ClinicalTrials.gov processed this record on November 20, 2014