Irradiated Bone MarrowPhase 1TrRaMM-TMINCT03963024
Treosulfan-TMI Conditioning and Rapamycin GvHD Prophylaxis Before Allo-HSCT
A Phase 1 study testing Conditioning treatment "Treosulfan-TMI", SCT and GvHD prophylaxis in people with Irradiated Bone Marrow and Transplant-Related Hematologic Malignancy, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
TrRaMM-TMI is a phase I trial to evaluate the feasibility and efficacy of an original sequential TMI/TrRaMM (Total Marrow Irradiation/Treosulfan-Rapamycin-Mycophenolate Mofetil) schedule in patients with hematological malignancies in advanced stage of disease undergoing an allogenic Stem Cell Transplant (SCT). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Irradiated Bone Marrow, Transplant-Related Hematologic Malignancy, Leukemia, Acute
- What is being tested?
- Conditioning treatment "Treosulfan-TMI", SCT and GvHD prophylaxis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteItaly
- Study dates
- 12 Feb 2014to 31 Jan 2019
- Phase
- Phase 1
- 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
- Patients with haematological malignancies such as
- any acute myeloid leukemia (AML) beyond Complete Remission (CR) 1
- any acute lymphoblastic leukemia (ALL) beyond CR1
- multiple myeloma (MM) at any relapse/progression, except refractory disease
- MM with unfavourable cytogenetic profile at diagnosis
- MM with less than a partial response (PR) after induction therapy
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- Karnofsky Index ≥ 80 %
- Adequate contraception in female patients of child-bearing potential.
- Written informed consent
- Availability of one of the following:
- A matched related or unrelated donor (MRD or MUD)
Who cannot join
- A hematopoietic cell transplantation-specific comorbidity index > 4
- Active non-controlled infectious disease at the moment of inclusion
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Impaired liver function (Bilirubin > 2.0 x upper normal limit; Transaminases > 3.0 x upper normal limit)
- Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
- Pleural effusion or ascites > 1.0 L
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- Pregnancy or lactation
- Known hypersensitivity to treosulfan and/or fludarabine and/or rapamycin
- Non-co-operative behaviour or non-compliance
- Psychiatric diseases or conditions that might impair the ability to give informed consent
- Previous spinal cord radiotherapy with dose ≥ 45 Gy equivalent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies
TrRaMM-TMI is a phase I trial to evaluate the feasibility and efficacy of an original sequential TMI/TrRaMM (Total Marrow Irradiation/Treosulfan-Rapamycin-Mycophenolate Mofetil) schedule in patients with hematological malignancies in advanced stage of disease undergoing an allogenic Stem Cell Transplant (SCT).
The aim is to determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule.
- Conditions
- Irradiated Bone Marrow, Transplant-Related Hematologic Malignancy, Leukemia, Acute, Multiple Myeloma, Graft Vs Host Disease
- Being tested
- Conditioning treatment "Treosulfan-TMI", SCT, GvHD prophylaxis
- Medical subject headings
- Leukemia, Multiple Myeloma, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conditioning treatment "Treosulfan-TMI"Drug
Treosulfan i.v.: 14 g/m²/d (day -6 to -4) Fludarabine i.v.: 30 mg/m²/d (day -6 to -2) Antithymocyte globulin (ATG)-Fresenius i.v.: 5/0 mg/kg (day -4 to -2) Mabthera i.v.: 200/0* mg/m2 (day -1) TMI: (10 Gy) 2 Gy bis in die (BID) (day -2 to -1) or TMI: (12 Gy) 2 Gy BID (day -3 to -1) or TMI: (14 Gy) 2 Gy BID (day -3 to -1)
SCTProcedure or surgery
Stem Cell Transplant
GvHD prophylaxisDrug
Rapamycin p.o.: 4 mg/d, (target 8-15 ng/ml) (starting day -7) Mycofenolate mofetile: 10 mg/kg tid, (Maximum dose 720 mg/tid) (starting from day 0)
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Treatment | Experimental | Conditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis; Receives: Drug: Conditioning treatment "Treosulfan-TMI"; Procedure: SCT; Drug: GvHD prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI)
To determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule
Measured: From administration of TMI (-5) to transplant
Rate of Survival post transplant
Evaluation of survival and engraftment
Measured: +30 days post transplantation
Secondary outcomes (5)
Efficacy - progression free survival (PFS)
PFS
Measured: End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Overall survival (OS)
OS
Measured: End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Relapse incidence (RI)
RI
Measured: End of total follow-up is 365 days after transplantation of the last patient included
Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)
Evaluation of incidence of NRM
Measured: Eon day +28, day +100 and +360
Evaluation of Transplant Safety
Cumulative of incidence and cumulative severity of GvHD
Measured: End of total follow-up is 365 days after transplantation of the last patient included
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start12 Feb 2014
- Primary completion31 Jan 2019
- Study completion31 Jan 2019
Why it stopped: low rate of enrolment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irradiated Bone MarrowStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ciceri Fabio, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03963024
- Sponsor's protocol ID
- 2013-002479-16
- Acronym
- TrRaMM-TMI
- Status last verified
- Oct 2020
- First submitted
- 21 May 2019
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies
- ClinicalTrials.gov ID
- NCT03963024
- Acronym / sponsor ID
- TrRaMM-TMI / 2013-002479-16
- Conditions
- Irradiated Bone Marrow, Transplant-Related Hematologic Malignancy, Leukemia, Acute, Multiple Myeloma, Graft Vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low rate of enrolment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 12 Feb 2014 (actual)
- Primary completion
- 31 Jan 2019 (actual)
- Study completion
- 31 Jan 2019 (actual)
- First posted
- 24 May 2019 (actual)
- 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.
TrRaMM-TMI is a phase I trial to evaluate the feasibility and efficacy of an original sequential TMI/TrRaMM (Total Marrow Irradiation/Treosulfan-Rapamycin-Mycophenolate Mofetil) schedule in patients with hematological malignancies in advanced stage of disease undergoing an allogenic Stem Cell Transplant (SCT).
The aim is to determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Treatment | Experimental | Drug: Conditioning treatment "Treosulfan-TMI", Procedure: SCT, Drug: GvHD prophylaxisConditioning treatment "Treosulfan+TMI"; SCT; GvHD prophylaxis; |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with haematological malignancies such as
- Karnofsky Index ≥ 80 %
- Adequate contraception in female patients of child-bearing potential.
- Written informed consent
- Availability of one of the following:
Key exclusion criteria (11 listed)
- A hematopoietic cell transplantation-specific comorbidity index > 4
- Active non-controlled infectious disease at the moment of inclusion
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Impaired liver function (Bilirubin > 2.0 x upper normal limit; Transaminases > 3.0 x upper normal limit)
- Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
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 |
|---|---|---|
| Conditioning treatment "Treosulfan-TMI"Treosulfan i.v.: 14 g/m²/d (day -6 to -4) Fludarabine i.v.: 30 mg/m²/d (day -6 to -2) Antithymocyte globulin (ATG)-Fresenius i.v.: 5/0 mg/kg (day -4 to -2) Mabthera i.v.: 200/0* mg/m2 (day -1) TMI: (10 Gy) 2 Gy bis in die (BID) (day -2 to -1) or TMI: (12 Gy) 2 Gy BID (day -3 to -1) or TMI: (14 Gy) 2 Gy BID (day -3 to -1) | Drug | Single Arm Treatment |
| SCTStem Cell Transplant | Procedure or surgery | Single Arm Treatment |
| GvHD prophylaxisRapamycin p.o.: 4 mg/d, (target 8-15 ng/ml) (starting day -7) Mycofenolate mofetile: 10 mg/kg tid, (Maximum dose 720 mg/tid) (starting from day 0) | Drug | Single Arm Treatment |
Primary outcome
Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI)
Time frame: From administration of TMI (-5) to transplant
To determine the maximum tolerated dose of TMI when combined with conditioning chemotherapy to transplant according to TrRaMM schedule
Rate of Survival post transplant
Time frame: +30 days post transplantation
Evaluation of survival and engraftment
5 secondary outcomes
Efficacy - progression free survival (PFS)
Time frame: End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Overall survival (OS)
Time frame: End of total follow-up is 365 days after transplantation of the last patient included
Efficacy - Relapse incidence (RI)
Time frame: End of total follow-up is 365 days after transplantation of the last patient included
Evaluation of Transplant Safety - incidence of non-relapse mortality (NRM)
Time frame: Eon day +28, day +100 and +360
Evaluation of Transplant Safety
Time frame: End of total follow-up is 365 days after transplantation of the last patient included
Results and safety
The study was stopped early (reason given: low rate of enrolment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Conditioning treatment "Treosulfan-TMI", SCT and GvHD prophylaxis in people with Irradiated Bone Marrow and Transplant-Related Hematologic Malignancy, run by IRCCS San Raffaele 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 11 inclusion and 11 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: stopped early, as of the sponsor's last update on 19 Oct 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: low rate of enrolment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the maximum tolerated dose of TMI (FEASIBILITY of TMI) (time frame: From administration of TMI (-5) to transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2020.