UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep

Summary

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

Conditions

• Acute Leukemia
• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia/Lymphoma
• Burkitt's Lymphoma
• Natural Killer Cell Malignancies
• Chronic Myelogenous Leukemia
• Myelodysplastic Syndrome
• Large-cell Lymphoma
• Hodgkin Lymphoma
• Multiple Myeloma
• Relapsed Chronic Lymphocytic Leukemia
• Relapsed Small Lymphocytic Lymphoma
• Marginal Zone B-cell Lymphoma
• Follicular Lymphoma
• Lymphoplasmacytic Lymphoma
• Mantle-cell Lymphoma
• Prolymphocytic Leukemia
• Bone Marrow Failure Syndromes
• Myeloproliferative Neoplasms/Myelofibrosis
• Biphenotypic/Undifferentiated/Prolymphocytic Leukemias
• MRD Positive Leukemia
• Leukemia or MDS in Aplasia
• Relapsed T-Cell Lymphoma
• Relapsed Multiple Myeloma
• Plasma Cell Leukemia

Interventions

DRUG

Fludarabine

Both Arms: 30 mg/m\^2 IV over 1 hour Day -6 to Day -2

DRUG

Cyclophosphamide

Arm 1: 50 mg/kg IV over 2 hours Day -6

DRUG

MMF

Both Arms: Mycophenolate mofetil (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. Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute graft versus host disease (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, do not stop MMF.

DRUG

Sirolimus

Both Arms: Adult Dosing: Sirolimus will be administered starting at Day -3 with 8-12 mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines. In the absence of acute GVHD sirolimus may be tapered starting at Day +100 and eliminated by Day +180 post-transplantation. Pediatric Dosing: Sirolimus will be administered starting on Day -3 with an oral loading dose of 10 mg followed by maintenance dosing of 2.5 mg/m\^2/day (Maximum total daily dose of 4mg) as per institutional guidelines. Target serum concentration goals are 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines.

RADIATION

TBI

Both Arms: 200 cGy on Day -1

BIOLOGICAL

Umbilical cord blood cell infusion

Both Arms: Day 0

BIOLOGICAL

ATG

Arm 2: 15 mg/kg IV every 12 hours Day -6 to Day -4

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Margaret MacMillan, MD, MSC · University of Minnesota

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-05-15

Primary Completion

2023-02-22

Completion

2024-02-22

FDA Drug

Yes

Countries

• United States

Study Locations