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

NCT ID: NCT00952237

Last Updated: 2018-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2011-04-30

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.

Conditions

Non-Hodgkin's Lymphoma; Hodgkin's Disease; Multiple Myeloma; Other Plasma Cell Dyscrasia (Waldenstrom, Amyloidosis); Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IL-2 and GM-CSF for Mobilization

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

Group Type: EXPERIMENTAL

GM-CSF

Intervention Type: DRUG

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.

IL-2

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Kenneth Meehan

Director, Bone Marrow Transplant Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth R Meehan, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

D0227

Identifier Type: -

Identifier Source: org_study_id