Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Thymoglobulin

Busulfan

Immunosuppressive Agents

Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

D-6: Fludara D-5: Fludara + Busilvex D-4: Fludara + Busilvex D-3: Fludara + Busilvex D-2: Fludara + Thymoglobuline D-1: Thymoglobuline D0: graft infusion

Fludarabine, Busulfan, Thymoglobuline

Mohamad Mohty, MD, PhD

The goal of this prospective study is to assess the overall mortality (whether related to relapse/progression or toxicity - TRM-) at one year after allogeneic stem cell transplantation prepared by a so-called reduced-toxicity "submyeloablative" conditioning regimen in patients with hematological malignancies.

Study of a Reduced-toxicity "Submyeloablative" Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies

Phase II Study of a Reduced-toxicity " Submyeloablative " Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies

Nantes University Hospital

Anne Omnès

Leukemia

Leukemia, Myeloid

Neoplasms by Histologic Type

Thiotepa

Antimetabolites

Reduced toxicity conditioning regimen (thiotepa, busulfan, fludarabine and ATG) followed by unrelated cord blood allogeneic stem cell transplant for high risk myeloïd malignancies.

The conditioning regimen will include:

* IV Thiotepa (5 mg/Kg/day for 2 days) (Day -7 and -6)
* IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)
* IV Busulfan (Busilvex 130 mg/m2/day for 3 days) (Day-5, -4 and -3)
* IV Anti-thymocyte globuline (Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

In patient with co-morbidities and/or older than 60 years, conditioning could be reduced after consulting the coordinator of the study:

* IV Thiotepa (5 mg/Kg/day for 2 days) (Day -6)
* IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)
* IV Busulfan (Busilvex 100 mg/m2/day for 3 days) (Day-5, -4 and -3)
* IV Anti-thymocyte globuline (Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

IV Thiotepa (5 mg/Kg/day for 2 days) (Day -7 and -6) or IV Thiotepa (5 mg/Kg/day for 2 days) (Day -6)

IV Thiotepa

IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)

IV Fludarabine

(Busilvex 130 mg/m2/day for 3 days) (Day-5, -4 and -3) or (Busilvex 100 mg/m2/day for 3 days) (Day-5, -4 and -3)

IV Busulfan

(Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

IV Anti-thymocyte globuline

Marie Thérèse RUBIO

Allogeneic cord blood stem cell transplantation is a potentially curative therapy for patients with haematological malignancies. We have extensive experience with the use of Cord Blood Transplantation (CBT) in patients with advanced myeloid malignancies. In adults however, the 40% Non-Relapse Mortality (NRM) rate observed after CBT conditioned with a myeloablative conditioning has encouraged the development of CBT with Reduced Intensity Conditioning (RIC). Our previous national CBT protocol (the Minicord French protocol - NCT00797758) showed that RIC CBT can reduce NRM, but relapse remains the main post-transplant event (\>30% at one year). Thus, the development of reduced toxicity rather than RIC conditioning for CBT is warranted in order to improve the outcome of such transplants by limiting NRM and reducing relapse rate. The Fludarabine, ATG and intensified doses of IV Busulfan (9.6 mg/Kg total dose) regimen is a well-established preparative regimen for reduced-intensity/toxicity conditioning prior to allogeneic stem cell transplantation using peripheral blood stem cells mobilized with G-CSF (ClinicalTrials.gov Identifier: NCT00841724). However, such regimen is likely not sufficient to allow for CB cell engraftment. Thiotepa is an alkylating and radio-mimetic agent with a large anti-tumor activity including leukemic cells, the ability to cross the blood-brain barrier and to improve engraftment of hematopoietic stem cells. This drug has been combined to usual conditioning regimen without increasing the toxicity but improving the engraftment rate and potentially reducing the relapse rate. Thus, in the context of adult CBT for high risk myeloid malignancies, we propose to prospectively evaluate a reduced toxicity conditioning based on the association of Thiotepa, Fludarabine, IV Busulfan and ATG with the objective to achieve acceptable NRM rates, and to allow for improved anti-leukemic control based on the cytotoxic component of the conditioning regimen itself, while waiting for the long term immune-mediated disease control (GVL effect).

Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies

Cumulative incidence of NRM at 12 months after transplantation : Safety and efficacy of the pre-transplant reduced toxicity conditioning regimen

Incidence of neutrophil engraftment (day and proportion of patients reaching neutrophils \>0.5x109/L); and platelets recovery (day and proportion of patients reaching platelets \> 20 x 109 / L without transfusion) after transplantation

Incidence and severity of acute GVHD (diagnosed and graded as standard criteria)

Incidence and severity of chronic GVHD (diagnosed and graded as standard criteria detailed )

Incidence of disease relapse at one year after transplantation (relapse is defined on the basis of morphologica evidence of leukemic cells in the bone marrow or other sites)

Evaluation of the quality of life (using a french translation of the FACT-BMT (version 4.0)

Assistance Publique - Hôpitaux de Paris

Heart and Blood Diseases

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Bortezomib

Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m\^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.

PK-directed dosing of IV busulfan for 4 days

IV busulfan

Single IV bortezomib at a dose of 1.3 mg/m\^2.

bortezomib

Autologous Hematopoietic Stem Cell Transplant (HSCT)

Study for the outcome and safety of individualized busulfan dosing with bortezomib for patients preparing for a second stem cell transplant to treat multiple myeloma.

Evaluation of six-month response in relapsed multiple myeloma subjects, who have had a prior autologous HSCT (greater than one year previously) receiving an IV busulfan-based conditioning regimen with the combination of pharmacokinetic (PK)-guided IV busulfan dosing and bortezomib, followed by a second autologous HSCT.

Assessment of the safety profile of this conditioning regimen will also be completed.

IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients

A Phase 2a Study of Once Daily Intravenous Busulfan With Bortezomib, Followed by an Autologous Hematopoietic Stem Cell Transplant (HSCT) in Subjects With Relapsed Multiple Myeloma After Prior Autologous HSCT

The percentage of participants reported in each disease category by International Myeloma Working Group (IMWG) uniform response criteria for Multiple Myeloma 6 months after autologous Hematopoietic stem cell transplant. Overall Disease Response categories were: \[stringent Complete Response (sCR)=CR + normal Free Light Chain (FLC) ratio + absence of clonal cells in bone marrow\], \[Complete Response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow\], \[Very Good Partial Response (VGPR)=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein + urine M-protein level \<100 mg/24 hour\], \[Partial Response (PR)=≥50% reduction of serum M-protein and reduction in 24 hour urine M-protein by ≥90% or to \<200 mg per 24 hour\], \[Stable Disease (SD)=Not meeting criteria for CR, VGPR, PR or progressive disease\] or \[Progressive Disease (PD)\].

Overall Survival was defined as the time in days from transplantation to death due to all causes.

Progression-free Survival (PFS) defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease (PD) by IMWG criteria. PD was defined as an Increase of ≥25% from the lowest response value in any one or more of the following: 1)Serum M-component and/or (the absolute increase must be ≥0.5 g/dL), 2)Urine M-component and/or (the absolute increase must be ≥200 mg/24 hr), 3)In patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL, 4)Bone marrow plasma cell percentage; the absolute percentage must be ≥10%, 5)Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas and/or 6)Development of hypercalcaemia that can be attributed solely to the plasma cell proliferative diso

Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.

The percent change in dose is relative to the busulfan dose administered at the Baseline Visit (Day -12 to -9) when a dose of 0.8 mg/kg was administered and on Day -5 when the Seattle Cancer Care Alliance recommended PK-adjusted dose was administered.

A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. Gas chromatography with mass selective detection (GC-MS) was used to determine the busulfan level in plasma. The ratio was calculated: AUC/Target AUC.

A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. GC-MS was used to determine the busulfan level in plasma. The percent difference was calculated between AUC and the Target AUC.

The percentage of participants with death related to transplant.

The Baltimore criteria for veno-occlusive disease was defined as the development of hyperbilirubinemia with serum bilirubin \> 2 mg/dl within 21 days after transplantation and at least 2 of the following clinical signs and symptoms: (1) hepatomegaly, usually painful, (2) \> 5% weight gain, or (3) ascites.

Otsuka Pharmaceutical Development & Commercialization, Inc.

Age, Continuous

Sex: Female, Male

Global Medical Affairs

sCR or CR or VGPR

PR or SD or PD

Not Assessed

Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

Percentage of Participants With Overall Disease Response at Month 6

Overall Survival

Percentage of Participants With Overall Survival Events

Progression-free Survival

Percentage of Participants With Progression-free Survival Events

Percent Change in IV Busulfan Dose

Ratio Area Under Curve (AUC)/Target AUC

Percent Difference Between Area Under Curve (AUC) and Target AUC

Safety population included all participants who received IV busulfan.

Percentage of Participants With Transplant-Related Mortality

Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria

Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the pharmacokinetic (PK)-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m\^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to hematopoietic stem cell transplant (HSCT).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of a Reduced-toxicity "Submyeloablative" Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies	NCT00841724	Hematological M...	Fludarabine, Bu...	18 Years - 65 Years	Nantes University Hospital
Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies	NCT02333838	Leukemia, Myelo...	IV Thiotepa IV Fludarabine IV Busulfan IV Anti-thymocy...	18 Years - 65 Years	Assistance Publique - Hôpitaux de Paris
IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients	NCT01009840	Multiple Myelom...	IV busulfan bortezomib Autologous Hema...	18 Years - 75 Years	Otsuka Pharmaceutical Development & Commercialization, Inc.
Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies	NCT02333838	Leukemia, Myelo...	IV Thiotepa IV Fludarabine IV Busulfan IV Anti-thymocy...	18 Years - 65 Years	Assistance Publique - Hôpitaux de Paris
IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients	NCT01009840	Multiple Myelom...	IV busulfan bortezomib Autologous Hema...	18 Years - 75 Years	Otsuka Pharmaceutical Development & Commercialization, Inc.
IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients	NCT01009840	Multiple Myelom...	IV busulfan bortezomib Autologous Hema...	18 Years - 75 Years	Otsuka Pharmaceutical Development & Commercialization, Inc.

Spots Global Cancer Trial Database for iv busulfan

Every month we try and update this database with for iv busulfan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for iv busulfan

Every month we try and update this database with for iv busulfan cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for iv busulfan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.