Thiotepa, Busulfan and Fludarabin for pt With Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas (TBF)

July 7, 2014 updated by: Benedetto Bruno, Azienda Ospedaliera San Giovanni Battista

Allogeneic Transplantation After a Conditioning With Thiotepa, Busulfan and Fludarabin for the Treatment of Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas: a Phase II Multi-Center Trial

The purpose of this study is to evaluate progression free survival, transplant-related morbidity (TRM) at day +100 and at +365, overall survival and incidence of acute and chronic GVHD in refractory/early relapsed aggressive B-cell non Hodgkin lymphomas patients treated with allogeneic Transplantation after a conditioning with Thiotepa, Busulfan and fludarabin.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In the present study, it is hypothesised that patients with aggressive B cell lymphomas refractory to or relapsed early (within 12 months) after the completion of standard first-line immunoProtocol TBF2012 Version 1, 20 Nov 2012 9 chemotherapy can benefit from de-bulking salvage therapy (i.e. R-DHAP + bortezomib) followed by an allograft to improve progression-free survival.

Patient inclusion criteria

  • Patients with refractory/relapsed aggressive B-cell non Hodgkin lymphomas after frontline therapy.
  • Patients with stable disease or partial or complete remission (PET-negative) after salvage therapy
  • Patients younger than 65 years old
  • A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered
  • Patient must be competent to give consent

Patient exclusion criteria

  • Patients treated with an autologous transplant as salvage therapy
  • Patients with progressive lymphomas despite conventional therapies
  • Patients with progressive lymphomas despite conventional therapies
  • Uncontrolled CNS involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant or breastfeeding

  • Organ dysfunction defined as follows:

    • Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
    • Pulmonary: DLCO <40% predicted
    • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4 the upper limit of normal
    • Renal: creatinine clearance <50 cc/min (24 hour urine Protocol TBF2012 Version 1, 20 Nov 2012 6 collection)
  • Karnofsky performance score < 60%
  • Patients with poorly controlled hypertension despite multiple antihypertensives
  • Documented fungal disease that is progressive despite treatment
  • Viral infections: HIV positive patients.
  • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded.
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
  • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
  • Patients with active non-hematologic malignancies (except nonmelanoma skin cancers).
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence. Donor inclusion criteria:
  • Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.
  • Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:
  • Age < 18 years.
  • Identical twin.
  • Pregnancy.
  • Infection with HIV.
  • Inability to achieve adequate venous access.
  • Known allergy to filgrastin (G-CSF).
  • Current serious systemic illness.

Donor inclusion criteria:

  • Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.
  • Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:
  • Age < 18 years.
  • Identical twin.
  • Pregnancy.
  • Infection with HIV.
  • Inability to achieve adequate venous access.
  • Known allergy to filgrastin (G-CSF).
  • Current serious systemic illness.

Donor inclusion criteria:

  • Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.
  • Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:
  • Age < 18 years.
  • Identical twin.
  • Pregnancy.
  • Infection with HIV.
  • Inability to achieve adequate venous access.
  • Known allergy to filgrastin (G-CSF).
  • Current serious systemic illness.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Torino, Italy, 10126
        • Recruiting
        • Citta della Salute e della Scienza di Torino
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Patient inclusion criteria:

  • Patients with refractory/relapsed aggressive B-cell non Hodgkin lymphomas after frontline therapy.
  • Patients with stable disease or partial or complete remission (PET-negative) after salvage therapy
  • Patients younger than 65 years old
  • A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered
  • Patient must be competent to give consent.

Patient exclusion criteria:

  • Patients treated with an autologous transplant as salvage therapy
  • Patients with progressive lymphomas despite conventional therapies
  • Patients with progressive lymphomas despite conventional therapies
  • Uncontrolled CNS involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant or breastfeeding

  • Organ dysfunction defined as follows:

    • Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
    • Pulmonary: DLCO <40% predicted
    • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal
    • Renal: creatinine clearance <50 cc/min (24 hour urine collection)
  • Karnofsky performance score < 60%
  • Patients with poorly controlled hypertension despite multiple antihypertensives
  • Documented fungal disease that is progressive despite treatment
  • Viral infections: HIV positive patients.
  • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded.
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
  • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers).
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence.

Donor inclusion criteria:

  • Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLA-mismatched (9/10 match) donors will also be considered.
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 mg/kg of body weight.
  • Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian).

Donor exclusion criteria:

  • Age < 18 years.
  • Identical twin.
  • Pregnancy.
  • Infection with HIV.
  • Inability to achieve adequate venous access.
  • Known allergy to filgrastin (G-CSF).
  • Current serious systemic illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
  • Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg)
  • Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg)
  • Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2)
Drug: Thiotepa
Other Names:
  • TEPADINA®
Drug: Busulfan
Other Names:
  • BUSILVEX®
Drug: Fludarabin
Other Names:
  • FLUDARA®
Procedure: transplant (HCT)
Transplant will be PBSCs collected as per institutional standard. A portion of the PBSC product will be removed for DLI that is equivalent to 3x10^7 CD3 cells/kg recipient weight and cryopreserved.
Radiation: Cytoreduction
Cytoreduction and /or radiation therapy will be given by the referring physician or the attending physician as determined on clinical grounds or to meet eligibility requirements of the protocol for patients with advanced malignancy or to reduce tumor bulk. However, no intensive chemotherapy can be given within three weeks before conditioning.
Drug: Immunosuppression
Day -3. Commence cyclosporine at 5.0 mg/kg PO Q12 hours, continue to day +50 and then taper by 5% per week until day +180.
Drug: Cyclosporine

CSP is given based on adjusted body weight, at 5.0 mg/kg PO q12 hours from day -3.

If there is nausea and vomiting at anytime during CSP treatment the drug should be given intravenously at the appropriate dose that was used to obtain a therapeutic level.

See guidelines for PO to IV conversion below.

Drug: Methotrexate
Day 1 15 mg Days 3, 6, 11 10 mg m2 day IV for GVHD prevention
Drug: ATG
(FOR UNRELATED TRANSPLANTS ONLY) Days -3, -2: 2.5 mg /kg/day
Other Names:
  • Anti-Human Thymocyte Globulin
Procedure: Collection and infusions of Donor PBSC
Collection and infusions of Donor PBSC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Progression free survival
Time Frame: 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years
Transplant-related morbidity (TRM) at day +100 and at +365
Time Frame: 1 year
1 year
Incidence of acute and chronic GVHD
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Ospedaliera San Giovanni Battista

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Benedetto Bruno, MD, Divisione di Ematologia-Città della Salute e della Scienza di Torino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2013

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 7, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TBF2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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