Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies
|ClinicalTrials.gov Identifier: NCT00824135|
Recruitment Status : Completed
First Posted : January 16, 2009
Last Update Posted : January 2, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Hematologic Malignancies||Drug: Clofarabine Procedure: Stem Cell Transplantation, Hematopoietic Other: OKT3 Drug: Thiotepa Drug: Melphalan Drug: Mycophenolate mofetil Drug: Rituximab Other: G-CSF||Phase 1|
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies|
|Study Start Date :||January 2009|
|Actual Primary Completion Date :||October 2012|
|Actual Study Completion Date :||December 2016|
Procedure: Stem Cell Transplantation, Hematopoietic
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
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
Other Name: Orthoclone OKT3Drug: 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)
Other Names:Drug: Rituximab
375 mg/m2 intravenous for 1 dose total
Other Name: RituxinOther: 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.
- To determine the MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system. [ Time Frame: 30 days ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00824135
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38119|
|Principal Investigator:||Brandon Triplett, MD||St. Jude Children's Research Hospital|