Informed Consent 
The principal investigator or one of his associates must explain verbally and in writing 
the nature of the study and the action of rhGM-CSF in such a manner that each patient or 
legal guardian of each patient is aware of the potential risks. The patient (or legal guardian) 
must also be informed that he/she (or the patient) may withdraw from the study at any time 
and for whatever reason, without prejudice to their future treatment If a legal guardian signs 
the informed consent, in accordance with Federal Regulations, he/she must sign the IRB- 
approved informed consent form in the presence of a witness. 
7. Study Synopsis 
Peripheral blood cells will be administered to 6 patients with autologous marrow 
followed by rhGM-CSF. Escalating doses of rhIL3 will be administered to the next 9 patients 
in groups of 3 (see schema of the study synopsis in Appendix A). Bone marrow will be 
harvested and stored prior to the initiation of rhIL3. Then 10 daily doses of rhIL3 will be 
j administered by 2 hour intravenous infusion in the Outpatient Department Just after the 7th 
dose of rhIL3 peripheral blood nucleated cells will be harvested by pheresis daily for 4 days and 
cryopreserved. Daily CD34 antigen analysis of CD34 + cells will be done and periodic samples 
for cell culture analysis will be drawn and progenitor assays will be performed to define the 
optimal times for peripheral blood harvesting in future studies. Patients will receive the 
preparative regimen as specified per FHCRC protocol Following the treatment regimen 
unstimulated bone marrow cells will be administered. Following this the rhIL3 stimulated 
peripheral blood nucleated cells (maximum cell dose 1 x 10’ kg) will be infused. Peripheral 
id cells will be collected approximately 24 hours after the last dose of rh!L3 just prior to the 
next dose of rhIL3. The half life of rhIL3 is only six min utes with none detectable two hours 
after administration so no free active rhIL3 will be present in the peripheral blood cell infusion. 
Within 2 hours of completing the infusion of the peripheral blood cells the first dose of rhGM- 
CSF will be given (250 Mg/kg/d ay). RhGM-CSF administration will continue until day 20. 
The clinical aspects of this study utilize unstimulated bone marrow stem cells to produce stable 
sustained engraftment and rhIL3 stimulated peripheral blood committed progenitor cells to 
produce early engraftment This study will also utilize the synergistic effects of rhGM-CSF with 
rhIL3 stimulated progenitor cells in an attempt to minimize days of severe neutropenia (ANC < 
100/mm 3 ). 
8. Study Design 
Peripheral blood cells will be ad minis tered to patients undergoing ABMT followed by 
rhGM-CSF. RhIL3 will be administered to 9 eligible patients (see Section 8) at escalating dose 
levels (2.0,5.0,10.0 pg/kg/day) by 2 hour intravenous infusion for 10 daily doses. Groups of 3 
patients will be treated at each dose level. When necessary all therapy (Le. treatment of 
infections) will be given according to standard procedures. Stimulated peripheral blood cells 
will be administered within 12 hours following infusion of unstimula ;ed bone marrow cells. Day 
0 will be the day marrow is infused. Drug safety-toxicity will be monitored according to Section 
16. All organ systems will be checked by daily clinical assessment a^J laboratory/radiologic 
tests. From the 28th day or from hospital discharge until 100 days post-transplantation the 
ients wili have follow-up monitoring on a weekly basis. 
Recombinant DNA Research, Volume 16 
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