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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00952237
First received: August 4, 2009
Last updated: July 26, 2012
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Multiple Myeloma
Other Plasma Cell Dyscrasia (Waldenstrom, Amyloidosis)
Leukemia
Drug: GM-CSF
Drug: IL-2
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: January 2003
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00952237

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Kenneth R Meehan, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00952237     History of Changes
Other Study ID Numbers: D0227
Study First Received: August 4, 2009
Last Updated: July 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Autologous Peripheral Blood Stem Cell Transplant
IL-2
GM-CSF

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Hodgkin Disease
Amyloidosis
Paraproteinemias
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Proteostasis Deficiencies
Metabolic Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014