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

NCT01786018 | Unknown Phase 2

• 1 other identifier: TBF2012
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B-cell Lymphoma Refractory

Keywords

Non Hodgkin lymphomas; Allogeneic Transplantation; Thiotepa; Busulfan; Fludarabin

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  2 years

Secondary Outcomes (3)

• Transplant-related morbidity (TRM) at day +100 and at +365

  1 year

• Overall survival

  2 years

• Incidence of acute and chronic GVHD

  2 years

Study Arms (1)

1

EXPERIMENTAL

* 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; Drug: Busulfan; Drug: Fludarabin; Procedure: transplant (HCT); Radiation: Cytoreduction; Drug: Immunosuppression; Drug: Cyclosporine; Drug: Methotrexate; Drug: ATG; Procedure: Collection and infusions of Donor PBSC

Interventions

Thiotepa DRUG

Also known as: TEPADINA®

1

Busulfan DRUG

Also known as: BUSILVEX®

1

Fludarabin DRUG

Also known as: FLUDARA®

1

transplant (HCT) PROCEDURE

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.

1

Cytoreduction RADIATION

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.

1

Immunosuppression DRUG

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.

1

Cyclosporine DRUG

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.

1

Methotrexate DRUG

Day 1 15 mg Days 3, 6, 11 10 mg m2 day IV for GVHD prevention

1

ATG DRUG

(FOR UNRELATED TRANSPLANTS ONLY) Days -3, -2: 2.5 mg /kg/day

Also known as: Anti-Human Thymocyte Globulin

1

Collection and infusions of Donor PBSC PROCEDURE

Collection and infusions of Donor PBSC

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera San Giovanni Battista: lead

Study Sites (1)

Città della Salute e della Scienza di Torino

Torino, 10126, Italy

RECRUITING

MeSH Terms

Interventions

Thiotepa; Busulfan; fludarabine phosphate; Transplantation; Hematocrit; Cytoreduction Surgical Procedures; Immunosuppression Therapy; Cyclosporine; Methotrexate; thymoglobulin

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Surgical Procedures, Operative; Hematologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Hemorheology; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Benedetto Bruno, MD

  Divisione di Ematologia-Città della Salute e della Scienza di Torino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benedetto Bruno, MD

CONTACT

+390116336728; benedetto.bruno@unito.it

Benedetto Bruno, MD

CONTACT

+390116336728; gismm2001@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 5, 2013
• First Posted: February 7, 2013
• Study Start: February 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: July 8, 2014

Record last verified: 2014-07

Locations

IT (1)