Clofarabine and Low Dose Total Body Irradiation as a Preparative Regimen for Stem Cell Transplant in Leukemia.

Summary

Stem cell transplant is an important therapeutic option for pediatric patients with relapsed or refractory leukemia. Although, full myeloablative transplants are widely used for patients with acute leukemia, myeloablative chemo-radiotherapy may not be feasible in some specific settings. These settings include 1) patients with pre-existing health issues and organ toxicities; 2) patients who have relapsed post-ablative transplant and need a second stem cell transplant; and 3) leukemia patients with advanced disease who have been heavily pre-treated. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. In this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with total body irradiation that can achieve durable donor engraftment without causing excessive toxicity.

Conditions

• Leukemia Lymphoblastic, Acute
• Acute Myeloid Leukemia
• Neoplasm Recurrent

Interventions

DRUG

Clofarabine

Clofarabine will be given as an intravenous infusion over 2 hours on days -6 though -2. The dose of Clofarabine will be assigned at study entry (30, 40 or 52 mg/m2).

RADIATION

Total Body Irradiation

Low dose (2 Gy) TBI will be administered from a linear accelerator at ≤ 20 cGy/min on day "0" according to institutional guidelines.

OTHER

Stem Cell Transplantation

Patients will be infused with 'unmanipulated' hematopoietic stem cells from a related or unrelated donor on day 0 of the treatment regimen according to institutional practice guidelines.

DRUG

Cyclosporine

Cyclosporine is given IV based on body weight at: * Age ≤ 6 years old: 6 mg/kg IV QD. in divided doses (e.g. 2 mg/kg q8hrs). * Age \> 6 years old: 3 mg/kg IV QD in divided doses (1.5mg/kg q12hrs) Cyclosporine should be started on day -1 after completion of Clofarabine. Levels should be maintained between 300-400 ng/ml.

DRUG

Mycophenolate Mofetil

MMF will be at 15 mg/kg, based on adjusted body weight, q 8 hours (45 mg/kg/day; max.3g/day) PO, or IV if indicated, from the evening of day 0 (i.e. first dose 4-6 hours following stem cell infusion) to day +40 post-transplant. Oral doses will be rounded to the nearest 250 mg (capsules are 250 mg). MMF is also available in oral suspension form. MMF will be given until day +40 post transplant and then tapered by 10% per week to be discontinued by day +90.

Sponsors & Collaborators

• Genzyme, a Sanofi Company

  collaborator INDUSTRY

• Therapeutic Advances in Childhood Leukemia Consortium

  lead OTHER

Principal Investigators

• Sandeep Soni, MD · Nationwide Childrens Hospital

• Haydar Frangoul, MD · Vanderbilt University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-01-29

Primary Completion

2014-08-31

Completion

2014-08-31

FDA Drug

Yes

Countries

• United States

Study Locations