Neoplasms

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Hematologic Neoplasms

Hematologic Diseases

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Anti-Infective Agents

Rituximab

Melphalan

Mycophenolic Acid

Thiotepa

Muromonab-CD3

Clofarabine

Antineoplastic Agents, Immunological

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Antimetabolites

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)

Stem Cell Transplantation, Hematopoietic

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

Muromonab-CD3

OKT3

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

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

Mycophenolate mofetil 600 mg/m2 intravenous two times a day

(continue for approximately 2 months or as clinically indicated)

Mycophenolate mofetil

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.

G-CSF

Brandon Triplett, MD

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.

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

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

Genzyme, a Sanofi Company

St. Jude Children's Research Hospital

TAK-285 50 mg tablet, orally, once or twice daily for three weeks, followed by seven days off. Dose escalation to maximum tolerated dose, with possibility of continuous dosing per cycle (daily dosing for four weeks without a break between cycles).

TAK-285 Dose Escalation Cohorts

Expanded cohort with dose and regimen dependent upon the safety profile of the maximally tolerated dose and schedule determined in the dose escalation phase of the study.

TAK-285 Recommended Phase 2 Dosing Cohort

Medical Monitor

The purpose of this study is to determine the safety and pharmacokinetics of TAK-285 in patients with advanced cancer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies	NCT00824135	Hematologic Mal...	Clofarabine Stem Cell Trans... OKT3 Thiotepa Melphalan Mycophenolate m... Rituximab G-CSF	- 21 Years	St. Jude Children's Research Hospital
Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies	NCT00824135	Hematologic Mal...	Clofarabine Stem Cell Trans... OKT3 Thiotepa Melphalan Mycophenolate m... Rituximab G-CSF	- 21 Years	St. Jude Children's Research Hospital
A Safety and Pharmacokinetic Study of TAK-285 in Patients With Advanced Cancer	NCT00535522	Cancer	TAK-285 Dose Es... TAK-285 Recomme...	18 Years -	Millennium Pharmaceuticals, Inc.
A Safety and Pharmacokinetic Study of TAK-285 in Patients With Advanced Cancer	NCT00535522	Cancer	TAK-285 Dose Es... TAK-285 Recomme...	18 Years -	Millennium Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for maximal tolerated dose