Immune Mobilization of Autologous Peripheral Blood Stem Cells Using Interleukin-2 and GM-CSF

April 23, 2018 updated by: Kenneth Meehan, Dartmouth-Hitchcock Medical Center
We postulate that the combination of IL-2 and GM-CSF immunotherapy will efficiently mobilize autologous peripheral blood stem cells and activated immune effector cells in patients with a hematologic malignancy. These activated effector cells will improve the immune function of the graft. These hypotheses will be tested using this proposed clinical trial to mobilize autologous peripheral blood stem cells pre-transplantation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All patients must have pathologic diagnosis of one of the following malignancies: Non-Hodgkin's Lymphoma, Hodgkin's Disease, Multiple Myeloma or other plasma cell dyscrasia (Waldenstrom, Amyloidosis), Leukemia (AML, ALL, CLL)
  • Prior Treatment: > 2 weeks prior to initiation of therapy.
  • Performance Status: Karnofsky > 70%
  • Age >18
  • Life Expectancy > 4 months
  • Bone Marrow: bone marrow biopsy and aspirate
  • Blood counts: The patient must have adequate bone marrow function, i.e. a total WBC of > 2,000/ul, a Hgb of > 7 mg/dl, and a platelet count of > 50,000/ul, unless this abnormality is believed to be due to the underlying disease.
  • Pulmonary function tests: DLCO > 55% predicted.
  • Cardiac: Left ventricular ejection fraction of > 40% by radionuclide scan or echocardiography.
  • Liver function tests (bilirubin, alkaline phosphatase, and SGOT/SGPT) < 3 x normal (unless believed to be elevated due to disease).
  • No significant co-morbid medical or psychiatric illness that would significantly compromise the patient's clinical care and chances of survival.
  • Informed Consent: Informed consent must be signed prior to the treatment. Patients must be aware of the neoplastic nature of their disease and willingly consent after being informed of the procedure to be followed, the nature of the therapy, alternatives, potential benefits, side effects, risks and discomforts. The patient is not deemed eligible if there is any other serious medical or psychiatric illness that would prevent informed consent. (Human protection committee approval of this protocol and a consent form is required.)

Exclusion Criteria:

  • Medical, social, or psychological factors which would prevent the patient from receiving or cooperating with the full course of therapy.
  • Evidence on physical exam, LP, CT, or MRI scans of CNS involvement with malignancy.
  • Uncontrolled or severe cardiovascular disease, including recent (< 6 months) myocardial infarction, congestive heart failure, angina (symptomatic despite optimal medical management), life-threatening arrhythmia, or hypertension or clinically significant obstructive/restrictive pulmonary disease.
  • Serology positive for HIV
  • History of seizures.
  • Concurrent or expected need for therapy with systemic corticosteroids (since systemic steroids may suppress the effects of IL-2).
  • Current and clinically significant pleural effusion, pericardial effusion, or ascites.
  • Positive pregnancy test or presence of lactation.
  • Uncontrolled active infection.
  • Documented hypersensitivity to any of the drugs used in the protocol.
  • No concomitant, ongoing malignancy that is life-threatening, based on PI's evaluation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IL-2 and GM-CSF for Mobilization
Immune Mobilization of Autologous Peripheral Blood Stem Cells Using Interleukin-2 and GM-CSF
Drug: GM-CSF

GM-CSF (Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor) The dose and duration of GM-CSF (7.5 mcg/kg/day) was selected. If used alone, this dose and duration would result in effective mobilization. GM-CSF will be started on Day #7 and will continue until completion of leukapheresis.

G-CSF will be started (5mcg/kg/d) on Day #7 and will be given each morning. G-CSF will continue until completion of leukapheresis.

Drug: IL-2

IL-2 dose escalation: IL-2 will be administered as a single daily subcutaneous injection each evening until completion of leukapheresis.

Escalation of the dose of IL-2 will be performed using the below schema with the following levels. Patients will be started on Level 1. (Level 0 is included since, if toxicity is meet in Level 1, the dose will be decreased to Level 0).

Level 0 - 3 x 105 i.u./m2/day for 11 days Level 1 - 6 x 105 i.u./m2/day for 11 days Level 2 - 1 x 106 i.u. /m2/day for 11 days as above Level 3 - 1.5 x 106 i.u. /m2/day for 11 days as above Level 4 - 2 x 106 i.u. /m2/day for 11 days as above

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Can IL-2 be administered with GM-CSF to efficiently mobilize autologous peripheral blood stem cells. This study will determine the maximum tolerated dose of IL-2 and the optimal biological dose with GM-CSF for stem cell mobilization.
Time Frame: 5 Years
5 Years

Secondary Outcome Measures

Outcome Measure
Time Frame
Will immune-mobilized stem cell products be well tolerated once infused into patients and will engraft normally following high-dose chemotherapy and APBSCT.
Time Frame: 5 Years
5 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Investigators

  • Principal Investigator: Kenneth R Meehan, MD, Dartmouth-Hitchcock Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

August 4, 2009

First Submitted That Met QC Criteria

August 4, 2009

First Posted (Estimate)

August 6, 2009

Study Record Updates

Last Update Posted (Actual)

April 25, 2018

Last Update Submitted That Met QC Criteria

April 23, 2018

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D0227

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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