NCT02167958

Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Rafic Farah, MD · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.

Detailed description

This is a pilot study to assess the safety and potential efficacy of haploidentical peripheral blood stem cell transplantation using a nonmyeloablative preparative regimen and post-transplant cyclophosphamide. The overall objective of this study is to collect the efficacy and safety data to provide the basis to decide whether a larger study of clinical efficacy is warranted in this setting.

Conditions

• Leukemia
• MDS
• Myelofibrosis
• Lymphoma

Interventions

Type	Name	Description
DRUG	Fludarabine	Fludarabine 30 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -6 through -2. Fludarabine will be dosed according to the recipient's Adjusted Ideal Body Weight (AIBW) unless AIBW is less than Ideal Body Weight (IBW). For decreased creatinine clearance (\< 61 mL/min) determined by the Cockcroft Formula: Cockcroft-Gault CrCl = (140-age) \* (Wt in kg) \* (0.85 if female) / (72 \* Cr) Fludarabine dosage should be reduced per standard of care.
DRUG	Cyclophosphamide	Pre-transplant Cy 14.5 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -6 and -5. Cy will be dosed according to the recipient's actual body weight unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the adjusted IBW Post-transplant Hydration prior to cyclophosphamide may be given according to Standard Practice Guidelines. Cyclophosphamide \[50mg/kg\] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cy will be dosed according to the recipient's actual body weight unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the adjusted IBW. Cyclophosphamide will be given as an IV infusion over 1-2 hours. .
DRUG	Mesna	Pre-transplant Mesna should be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of mesna is equal to 100% of the total daily dose of cyclophosphamide. Post-transplant Mesna should be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of mesna is equal to 100% of the total daily dose of cyclophosphamide.
RADIATION	Total Body Irradiation	200 cGy will be administered in a single fraction on Day -1 via linear accelerator.
OTHER	Hematopoietic stem cell infusion	Donors who consent to PBSC donation will receive 5 daily doses of G-CSF, 10 μg/kg/day by subcutaneous injection commencing on day -5. PBSC's will be collected in the afternoon of day -1, stored at 4C overnight, and infused as soon as possible on day 0. If the collection on day -1 contains less than 5.0 X 106 CD34+ cells per kg recipient weight, a second collection will be performed the following morning and infused on day 0. Quantitation of CD34 and CD3 cells will be performed by the Cellular Therapy Lab. For all patients, the target number of CD34 cells to be infused should be 5-6 X 106 cells per kg recipient weight. PBSC in excess of 6.0 x 106 CD34 cells/kg recipient weight may be cryopreserved.
DRUG	Tacrolimus	Tacrolimus will be given at a dose of .03 mg/kg IV over 24 hours. Tacrolimus will be changed to a PO dosing schedule once a therapeutic level is achieved and the patient is tolerating PO. Whole bloodblood levels of tacrolimus will be measured around Day 7 and then should be checked at least weekly thereafter and the dose adjusted accordingly to maintain a level of 5-10 ng/mL. Tacrolimus will be discontinued after the last dose around Day 180, or may be continued if active GVHD is present. Cyclosporine (target concentration 200-400 ng/ml) may be substituted for tacrolimus if the patient is intolerant of tacrolimus.
DRUG	Mycophenolate	Either the sodium salt of mycophenolate or mycophenolate mofetil (MMF) may be used as prophylaxis of GvHD and will be dosed by actual bodyweight. Only MMF is available as IV formulation. Sodium mycophenolate will be given at a dose of 10mg/kg PO TID rounded to the nearest number of 180mg tablets. MMF will be given at a dose of 15 mg/kg PO TID. The maximum total daily dose should not exceed 2160 mg (sodium salt) or 3 grams (mofetil). Mycophenolate prophylaxis will be discontinued after the last dose on Day 35, or may be continued if active GVHD is present.
DRUG	G-CSF	G-CSF will be given beginning on Day 5 at a dose of 5 mcg/kg/day (rounding to the nearest vial dose is allowed), until the absolute neutrophil count (ANC) is \> 1,000/mm3 for three consecutive days.

Timeline

• Start date: 2015-02-11
• Primary completion: 2019-09-21
• Completion: 2019-09-21
• First posted: 2014-06-19
• Last updated: 2019-10-15

Locations

1 site across 1 country: United States