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

Sponsor

Dartmouth-Hitchcock Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00952237

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

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

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

Outcome Measures

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. [5 Years]

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. [5 Years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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