NCT02661035

Allo HSCT Using RIC for Hematological Diseases

Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) for the Treatment of Hematological Diseases [MT2015-32]

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 156 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 75 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. The primary objective is to evaluate rates of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD with an updated GVHD prophylaxis of tacrolimus and mycophenolate mofetil (MMF) with a non-myeloablative preparative regimen in persons with hematologic malignancies.

Conditions

• Acute Myelogenous Leukemia
• Acute Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Plasma Cell Leukemia
• Myelodysplastic Syndromes
• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• B-Cell Lymphoma
• Follicular Lymphoma
• Lymphoplasmacytic Lymphoma
• Mantle-Cell Lymphoma
• Prolymphocytic Leukemia
• Lymphoblastic Lymphoma
• Burkitt's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Myeloproliferative Syndromes
• Hematological Diseases

Interventions

Type	Name	Description
DRUG	Allopurinol	300 mg/day (for peds -150 mg/m\^2/day), day -6 and continue through day 0 or longer if clinically indicated
DRUG	Fludarabine	30 mg/m\^2 IV over 1 hour, day -6, -5, -4, -3 and -2
DRUG	Cyclophosphamide	50 mg/kg IV over 2 hours, day -6
DRUG	ATG	Only for patients with an unrelated donor (URD) and NO multi-agent chemotherapy 3 months prior to transplant. ATG will be administered IV every 12 hours for 6 doses on days -6, -5, and -4 according to institutional guidelines. Methylprednisolone 1 mg/kg IV administered immediately prior to each dose of ATG (6 doses).
RADIATION	TBI	All patients who have had previous radiation therapy or TBI will be seen by Radiation Oncology prior to entrance on the protocol for approval for additional 200 cGy of TBI. TBI may be delivered by local guidelines provided the effective dose is equivalent to what is recommended in the TBI Guidelines. The dose of TBI will be 200 cGy given in a single fraction on day -1.
DRUG	Tacrolimus	All patients will receive tacrolimus therapy beginning on day -3. Initial dosing of tacrolimus will be 0.03 - 0.05 mg/kg/day IV; if the recipient body weight is \<40 kg, dosing will be 3 times daily, and if ≥ 40 kg, twice daily or per current institutional guidelines. An attempt will be made to maintain a trough level of 5-10 ng/mL and subsequent dose modifications will be provided by the pharmacist. Once the patient can tolerate oral medications and has a reasonable oral intake, tacrolimus will be converted to an oral form based on the current IV dose providing normal renal and hepatic function and no major drug interactions. The timing of the tacrolimus taper will be at the discretion of the treating physician, but in general: * Taper begins at day +100 +/- 10 days, if the patient is stably engrafted and has no active GVHD. * Taper to zero by reducing dose by approximately 10% a week (rounded to nearest pill size), with a goal to discontinue by month 6 post-HCT.
DRUG	MMF	3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (\>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies. MMF will stop at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count \[ANC) ≥ 0.5 x 109 /L\]). If no donor engraftment, MMF will continue as long as clinically indicated.
BIOLOGICAL	Peripheral Blood Stem Cells	On day 0, patients will receive an allogeneic transplant using PBSC which are CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.
BIOLOGICAL	Related or Unrelated Bone Marrow Cells	On day 0, a target dose of 3 x 10\^8 nucleated cells/kg recipient weight will be collected. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.

Timeline

• Start date: 2017-03-09
• Primary completion: 2023-04-17
• Completion: 2023-05-29
• First posted: 2016-01-21
• Last updated: 2023-09-21

Locations

1 site across 1 country: United States