NCT00824135

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The primary objective of this trial is to determine the maximum tolerated dose of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical stem cell transplant with an engineered graft depleted of CD3+ cells. Study participants will children and young adults with refractory hematologic malignancies. Secondary objectives include the following: * To describe the one-year overall survival (OS) and event-free survival (EFS) rates in these study participants. * To determine the time to hematopoietic recovery and donor cell engraftment following this study treatment. * To estimate the cumulative incidence of relapse in study participants. * To estimate the incidence of overall grade II-IV and grade III-IV acute GVHD and the rate of chronic GVHD. * To estimate the incidence and describe the causes of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post HSCT. * To explore the biologic significance of soluble interleukin-2 (IL-2) receptor, tumor necrosis factor (TNF), and lymphocyte reconstitution (qualitative and quantitative, V beta spectratyping, TREC

Conditions

• Hematologic Malignancies

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2009-01-01
• Primary completion: 2012-10-01
• Completion: 2016-12-01
• First posted: 2009-01-16
• Last updated: 2017-01-02

Locations

1 site across 1 country: United States