Allo HSCT Using RIC for Hematological Diseases

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

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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Erica Warlick, MD · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-03-09

Primary Completion

2023-04-17

Completion

2023-05-29

Countries

• United States

Study Locations