Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies

Summary

Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. The investigators institution has utilized mismatched family member donors for these patients for several reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer (NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain patient groups; and, (4) no other curative treatment options are available.

In the present trial, the investigators propose a novel conditioning regimen using clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.

Conditions

• Hematologic Malignancies

Interventions

DRUG

Clofarabine

One dose intravenously every 24 hrs for five days total. Dose level 1 Clofarabine 40 mg/m2/day intravenous Dose level 2 Clofarabine 45 mg/m2/day intravenous Dose Level 3 Clofarabine 50 mg/m2/day intravenous

PROCEDURE

Stem Cell Transplantation, Hematopoietic

Haploidentical Hematopoietic Stem Cell Transplantation (two infusions, one on day 0 and the other on day +1)

OTHER

OKT3

Start at 0.0125 mg/kg intravenous once a day, taper dose down incrementally and discontinue after 17 days total Muromonab-CD3

DRUG

Thiotepa

5 mg/kg/day intravenous every 12 hours (2 doses total)

DRUG

Melphalan

60mg/m2 intravenous every 12 hours for 2 doses total.

DRUG

Mycophenolate mofetil

Mycophenolate mofetil 600 mg/m2 intravenous two times a day (continue for approximately 2 months or as clinically indicated)

DRUG

Rituximab

375 mg/m2 intravenous for 1 dose total

OTHER

G-CSF

G-CSF 5 mcg/kg/day subcutaneous or intravenous until ANC greater than 2.000/mm3 for 2 consecutive days and then as clinically indicated.

Sponsors & Collaborators

• Genzyme, a Sanofi Company

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Brandon Triplett, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-01-31

Primary Completion

2012-10-31

Completion

2016-12-31

Countries

• United States

Study Locations