LymphomaPhase 2NCT02049580
Reduced Intensity Conditioning (RIC) Regimen and Post-transplant Cyclophosphamide in Haploidentical Bone Marrow Transplantation in in Patients With Poor Prognosis Lymphomas
A Phase 2 study testing Thiotepa, Fludarabine and Cyclophosphamide in people with Lymphoma, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Study to test feasibility and efficacy of T-replete Bone Marrow (BM), infused after a RIC regimen and post-transplantation Cyclophosphamide (Cy), in patients with poor prognosis lymphomas. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Thiotepa, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2013to Nov 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Presence of HLA-matched, related donor (HLA-A, -B, -DRB1)
- Presence of matched unrelated donor (10/10), available on time.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection
- Evidence of progression of clinical symptoms or radiologic findings.
- Prior allogeneic hematopoietic stem cell transplant.
- Central Nervous System (CNS) lymphoma localization
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Rozzano, MI, 20089
Luca Castagna, MD, +39028224 ext. 4587, luca.castagna@humanitas.it
Luca Castagna, MD
About this study
Official title: Multi-center, Phase II Study to Assess the Safety and Efficacy of Haploidentical Bone Marrow Transplantation Using Reduced Intensity Conditioning(RIC)Regimen and Post-transplant Cyclophosphamide,in Patients With Poor Prognosis Lymphomas
Study to test feasibility and efficacy of T-replete Bone Marrow (BM), infused after a RIC regimen and post-transplantation Cyclophosphamide (Cy), in patients with poor prognosis lymphomas.
Read the detailed description
Allogeneic stem cell transplantation (ALLO) is the treatment of choice for many hematological diseases. However, HLA identical donor (sibling or unrelated) is available for 50-60% of patients and alternative donors are needed. Haploidentical donors have been used for many years, mostly after extensive T-cell depletion of peripheral stem cell, to avoid Graft Versus Host Disease (GVHD). Recently, promising data have been reported with haploidentical transplantation using T-replete bone marrow (BM) and high-dose cyclophosphamide (Cy) post-transplantation. However, the conditioning regimen did not contain drugs active against hemopathies, enhancing the relapse risk.
In this study, the investigators want to test the feasibility and efficacy of T-replete BM, infused after a RIC regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases.
The RIC regimen consisted of modified regimen used in different studies conducted in Italy on behalf GITMO.
- Conditions
- Lymphoma
- Being tested
- Thiotepa, Fludarabine, Cyclophosphamide
- Keywords
- lymphoma
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiotepaDrug
Also called Tepadina
Thiotepa (10 mg/kg /day) will be administered every 12 h, at day -6
FludarabineDrug
Also called Fludara
Fludarabine (30mg/m2/day x 4 days) will be dosed according to renal function. For decreased creatinine clearance (CCr) (≤ 61 mL/min) Fludarabine dosage should be reduced as follows:
CCr 46-60 mL/min, fludarabine = 24 mg/ m2/day
CyclophosphamideDrug
Also called Endoxan
Pre-transplantation Cyclophosphamide(Cy) 30 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -5.
Cy will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the Adjusted IBW (AIBW)
Cyclophosphamide [50 mg/kg/day IBW] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).
| Study group | Role | What they receive |
|---|---|---|
| RIC regimen | Experimental | Thiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation. Receives: Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Procedure activity
1-year Progression Free Survival (PFS) to evaluate the activity of the procedure (taking into account an excess of toxicity). It is assumed that at 1-year a proportion of patients progression free of 20% or lower will be considered to be clinically unworthy, whereas a proportion of 40% or higher will be assumed to be of potential interest.
Measured: 1 year
Secondary outcomes (8)
Neutrophils recovery
Neutrophils will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated
Measured: 1 year
Platelets recovery
Platelets will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated
Measured: 1 year
Incidence of graft failure
Measured: 1 year
Cumulative incidence of acute and chronic GVHD
Measured: 1 year
Incidence of infections
Possible infections will be monitored for a time period of 1 year post-transplantation and then if clinically required
Measured: 1 year
Cumulative incidence of relapse/progression
Measured: 1 year
Treatment related mortality (TRM)
Measured: 1 year
Immunological reconstitution
T, B and NK subsets will be analysed in deep using cytofluorimetry and functional tests.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study startJul 2013
- Primary completionAug 2016 (estimated)
- Study completionNov 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luca Castagna, MD, Principal investigator, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049580
- Sponsor's protocol ID
- ONC-2011-005
- Status last verified
- Jan 2014
- First submitted
- 28 Jan 2014
- Last updated
- 30 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, Gandolfi S, Tentorio P, Sarina B, Timofeeva I, Santoro A, Carlo-Stella C, Bruno B, Carniti C, Corradini P, Gostick E, Ladell K, Price DA, Roederer M, Mavilio D, Lugli E. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood. 2015 Apr 30;125(18):2855-64. doi: 10.1182/blood-2014-11-608406. Epub 2015 Mar 5.
PubMed 25742699
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Phase II Study to Assess the Safety and Efficacy of Haploidentical Bone Marrow Transplantation Using Reduced Intensity Conditioning(RIC)Regimen and Post-transplant Cyclophosphamide,in Patients With Poor Prognosis Lymphomas
- ClinicalTrials.gov ID
- NCT02049580
- Acronym / sponsor ID
- ONC-2011-005
- Conditions
- Lymphoma
- Keywords
- lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Nov 2016 (estimated)
- First posted
- 30 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to test feasibility and efficacy of T-replete Bone Marrow (BM), infused after a RIC regimen and post-transplantation Cyclophosphamide (Cy), in patients with poor prognosis lymphomas.
Detailed description
Allogeneic stem cell transplantation (ALLO) is the treatment of choice for many hematological diseases. However, HLA identical donor (sibling or unrelated) is available for 50-60% of patients and alternative donors are needed. Haploidentical donors have been used for many years, mostly after extensive T-cell depletion of peripheral stem cell, to avoid Graft Versus Host Disease (GVHD). Recently, promising data have been reported with haploidentical transplantation using T-replete bone marrow (BM) and high-dose cyclophosphamide (Cy) post-transplantation. However, the conditioning regimen did not contain drugs active against hemopathies, enhancing the relapse risk.
In this study, the investigators want to test the feasibility and efficacy of T-replete BM, infused after a RIC regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases.
The RIC regimen consisted of modified regimen used in different studies conducted in Italy on behalf GITMO.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RIC regimen | Experimental | Drug: Thiotepa, Drug: Fludarabine, Drug: CyclophosphamideThiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- Presence of HLA-matched, related donor (HLA-A, -B, -DRB1)
- Presence of matched unrelated donor (10/10), available on time.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThiotepaAlso: TepadinaThiotepa (10 mg/kg /day) will be administered every 12 h, at day -6 | Drug | RIC regimen |
| FludarabineAlso: FludaraFludarabine (30mg/m2/day x 4 days) will be dosed according to renal function. For decreased creatinine clearance (CCr) (≤ 61 mL/min) Fludarabine dosage should be reduced as follows: CCr 46-60 mL/min, fludarabine = 24 mg/ m2/day | Drug | RIC regimen |
| CyclophosphamideAlso: EndoxanPre-transplantation Cyclophosphamide(Cy) 30 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -5. Cy will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the Adjusted IBW (AIBW) Cyclophosphamide [50 mg/kg/day IBW] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume). | Drug | RIC regimen |
Primary outcome
Procedure activity
Time frame: 1 year
1-year Progression Free Survival (PFS) to evaluate the activity of the procedure (taking into account an excess of toxicity). It is assumed that at 1-year a proportion of patients progression free of 20% or lower will be considered to be clinically unworthy, whereas a proportion of 40% or higher will be assumed to be of potential interest.
8 secondary outcomes
Neutrophils recovery
Time frame: 1 year
Platelets recovery
Time frame: 1 year
Incidence of graft failure
Time frame: 1 year
Cumulative incidence of acute and chronic GVHD
Time frame: 1 year
Incidence of infections
Time frame: 1 year
Cumulative incidence of relapse/progression
Time frame: 1 year
Treatment related mortality (TRM)
Time frame: 1 year
Immunological reconstitution
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2014.
- Derived from this study: PubMed 25742699Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, Gandolfi S, Tentorio P, Sarina B, Timofeeva I, Santoro A, Carlo-Stella C, Bruno B, Carniti C, Corradini P, Gostick E, Ladell K, Price DA, Roederer M, Mavilio D, Lugli E. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood. 2015 Apr 30;125(18):2855-64. doi: 10.1182/blood-2014-11-608406. Epub 2015 Mar 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luca Castagna, MD principal investigator
Istituto Clinico Humanitas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Thiotepa, Fludarabine and Cyclophosphamide in people with Lymphoma, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luca Castagna, MD (+39028224 ext. 4587, luca.castagna@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Procedure activity (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02049580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2014.