Total Marrow Irradiation for Refractory Acute Leukemia

Summary

RATIONALE: Giving chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.

Conditions

• Acute Lymphoblastic Leukemia
• Myelodysplastic Syndrome
• Multiple Myeloma

Interventions

DRUG

cyclophosphamide

60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg

DRUG

cyclosporine

Beginning on Day -3 pre-transplant maintaining a level of \>200 ng/mL. CSA dosing will be monitored and altered as clinically appropriate by Pharm D or physician, and discontinue at approximately day + 180 post-transplant.

DRUG

Fludarabine

25 mg/m2/day intravenous as a 1 hour infusion for consecutive 3 days pre-transplant, total dose 75 mg/m2

DRUG

mycophenolate mofetil

Beginning on day -3, use intravenous route between days -3 and +5, followed by oral administration on Day +6 through +30, if tolerated. 15mg/kg/dose for patients \<40 kg, 3 gm/day for patients \>40 kg.

RADIATION

total marrow irradiation

Dose escalating schedule per Cohort (TMI: 300 cGy) once daily.

PROCEDURE

umbilical cord blood transplantation

product will be infused via intravenous drip on Day 0 according to current University of Minnesota guidelines for Umbilical Cord Blood Grafts

BIOLOGICAL

Granulocyte colony-stimulating factor

5 mcg/kg/day intravenous or subcutaneous based on body weight beginning on Day +1 after umbilical cord blood infusion until absolute neutrophil count exceeds 2.5 x 10\^9/L for 3 consecutive days.

BIOLOGICAL

HLA-matched related donor bone marrow

Related donor bone marrow or mobilized stem cells will be collected (target cell dose 5x10\^8 nucleated cells/kg recipient weight, minimum 3x10\^8 nucleated cells/kg recipient weight) and infused without processing on day 0 according to University of Minnesota Blood and Marrow Transplant Program guidelines.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• John Wagner, MD · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-08-31

Primary Completion

2016-11-30

Completion

2016-12-31

Countries

• United States

Study Locations