Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

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

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Etoposide

Cytarabine

Etoposide phosphate

CR Cohort: high-risk ALL in CR and standard-risk ALL in the status of ≥CR2

CR Cohort will receive conditioning regimen of TBI+CY+VP-16: TBI: 4.5Gy/d, -5d, -4d; CY: 60mg/kg/d, -3d, -2d; VP-16: 15mg/kg/d, -3d, -2d

TBI+CY+VP-16

NR Cohort will receive conditioning regimen of FA+TBI+CY+VP-16: Flu: 35mg/m2/d: -10\~-6d; AraC: 1g/m2/d, -10d\~-6d; TBI: 4.5Gy/d, -5d,-4d; CY:60mg/kg/d, -3d, -2d; VP-16: 15mg/kg, -3d, -2d

FA+TBI+CY+VP-16

Qifa Liu, MD

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials.

High relapse and transplantation-related-mortality still remains great challenge for HSCT of adult ALL, which both range between 25% and 30%. Recently, risk-adapted indication and optimization of conditioning regimen are highlighted, which aiming to reduce TRM and relapse rate, respectively.City of Hope National Medical Center studied the substitution of etoposide (VP-16) for CY in the treatment of ALL patients receiving HCT. The result suggested that etoposide and TBI are associated with a decreased relapse rate following transplantation for ALL, compared with those receiving CY and TBI. Japanese and Germany reports pronounced the advantage of VP-16 in intensified regimen for adult ALL. On the same time, the investigators previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, the investigators speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

In the first decade of the new millennium, multiple studies have begun to change our thinking about the treatment of adults with acute lymphoblastic leukemia (ALL). In pediatric patients cure rates in the range of 80% to 90% are now attainable. While adult patients with ALL now have a 90% complete remission (CR) with modern chemotherapy, most patients will relapse, and leukemia-free survival with 3 to 7 years of follow-up in large series is only in the range of 30% to 40%. The poor outcome of chemotherapy in adults with ALL as compared to children relates to multiple factors, including poor tolerance of intensive courses of chemotherapy and a higher incidence of poor prognostic subtypes of ALL such as Philadelphia chromosome-positive ALL and a lower incidence of favorable subtypes such as the t (12; 21).

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. Adult regimens are typically less intense than pediatric regimens. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials. These results have prompted new studies where pediatric ALL regimens have been adapted to the treatment of younger adults. With short follow-up, GRAALL-2003 reports suggest EFS and OS outcomes in the range of 60%. This improved outcome was more pronounced in the standard-risk patients with a donor who had an OS at 5 years of 69%. On the same time, our previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, we speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia

A Prospective Study of Intensified Conditioning Regimen With High-Dose-Etoposide for Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in China

Fujian Medical University Union Hospital

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Third Affiliated Hospital, Sun Yat-Sen University

Xiangya Hospital of Central South University

Nanfang Hospital, Southern Medical University

Professor

Symptoms and General Pathology

Syndrome

Graft vs Host Disease

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Juvenile

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Acute

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Homologous Wasting Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Anticonvulsants

Antiemetics

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Dermatologic Agents

Reproductive Control Agents

Cyclophosphamide

Lorazepam

Methotrexate

Busulfan

Total Body Irradiation (TBI) 1200 cGy will be given on days -8,-7,-6 and -5 in eight sessions, delivering 150cGy in each session.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3, -2.

Myeloablative Chemotherapy Regimen for Lymphoid Malignancies or Cord Blood Unit Recipients

Busulfan administration:

* For children \>/= 4 years of age, Busulfan 0.8 mg/kg/dose will be given every 6 hours over days -8,-7, -6, and -5 for a total of 16 doses.
* For children \< 4 years of age, Busulfan 1 mg/kg/dose will be given every 6 hours over days -8, -7, -6, -5 for a total of 16 doses.
* Pharmacokinetic analysis will guide dose modifications targeted to receive an average AUC of 800-1200 microMols\*min for the 16 doses.

Lorazepam (0.05 mg/kg) IV will be administered one half hour before the initial dose of Busulfan is given and every 6 hours through day -4.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3 and -2.

Myeloablative Chemotherapy Regimen for Non-Cord Blood Unit Recipients with Myeloid Malignancies

Hematopoietic progenitor cells (HPCs) will be infused on day 0. Source of cells may be bone marrow, peripheral blood cells, or cord blood units, from matched related or unrelated donors.

Hematopoietic Progenitor Cell Transplantation (HPCT)

Patients with prior CNS disease over the age of 1 year will be treated with 600 cGy of cranial irradiation in addition to 1200 cGy of TBI.

Patients diagnosed with ALL with CNS disease (at the time of diagnosis or relapse) \< 1 year of age will receive CNS treatment as Intrathecal Methotrexate as follows:

* Infants ≤ 1 year of age at the time of Intrathecal Therapy will receive a dosing of 7.5 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count
* Children 1-2 years of age at the time of Intrathecal Therapy will receive 8 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count

CNS radiation treatment for ALL with prior CNS disease patients

Morris Kletzel, MD

Terriss Conterato

The purpose of this study is to show that myeloablative hematopoietic progenitor cell transplantation (HPCT) continues to offer acceptable disease-free survival for select patients requiring HPCT.

Myeloablative hematopoietic progenitor cell transplantation (HPCT) remains the standard of care for patients requiring HPCT. The purpose of this study is to evaluate the morbidity and mortality of myeloablative HPCT at Children's Memorial Hospital. It will also look to determine the toxicity of a single conditioning regimen consisting of total body irradiation (TBI), etoposide (VP-16), and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or with transplant eligible myeloid malignant conditions who are receiving cord blood units, or to determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units.

Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

Ann & Robert H Lurie Children's Hospital of Chicago

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
Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia	NCT01457040	Acute Lymphobla... Stem Cell Trans...	TBI+CY+VP-16 FA+TBI+CY+VP-16	14 Years - 65 Years	Nanfang Hospital, Southern Medical University
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
Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia	NCT01457040	Acute Lymphobla... Stem Cell Trans...	TBI+CY+VP-16 FA+TBI+CY+VP-16	14 Years - 65 Years	Nanfang Hospital, Southern Medical University
Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies	NCT00619879	Leukemia, Myelo... Leukemia, Lymph... Leukemia, Myelo... Myeloproliferat... Lymphoma, Malig...	Myeloablative C... Myeloablative C... Hematopoietic P... CNS radiation t...	- 21 Years	Ann & Robert H Lurie Children's Hospital of Chicago
Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia	NCT01457040	Acute Lymphobla... Stem Cell Trans...	TBI+CY+VP-16 FA+TBI+CY+VP-16	14 Years - 65 Years	Nanfang Hospital, Southern Medical University

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