Hematologic MalignanciesPhase 1/2NCT01350258
Bone Marrow Transplant Using a Reduced Intensity Regimen That is Given in Two Steps
A Phase 1/2 study testing Fludarabine, Thiotepa and Total Body Irradiation (TBI) in people with Hematologic Malignancies and Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial summary
This is a research study involving the treatment of patients with hematological cancers with allogeneic (cells from a donor) hematopoietic stem cell transplant (HSCT). HSCT is often referred to as bone marrow transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies, Acute Leukemia, Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes
- What is being tested?
- Fludarabine, Thiotepa and Total Body Irradiation (TBI)
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Aug 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as:
- Acute leukemia in 3rd or greater CR or with persistent disease
- Myelodysplastic syndrome (MDS) other than RA or RARS subtypes.
- Hodgkin's or Non-Hodgkin's lymphoma in 3rd or greater remission or with persistent disease.
- Myeloma in 3rd or greater remission or with less than PR to most recent therapy.
- Chronic myelogenous (or myeloid) leukemia (CML) resistant to STI therapy
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- Patients must have a related donor who is at least a 4 antigen match at the HLA-A; B; C; DR loci.
- Patients must adequate organ function:
- LVEF of > or = 50%
- DLCO > or = 50% of predicted corrected for hemoglobin
- Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT < or = 2.5X upper limit of normal
- GFR of > or = 60 mL/min/1.73m2
- Performance status > or = 80% (TJU Karnofsky) for patients > or = 60 years old or > or = 70% for patients < 60.
- HCT-CI Score < or = 4 points for patients > or = 60 years old or < or = 5 points for patients < 60.
- Patients must be willing to use contraception if they have childbearing potential
- Able to give informed consent
Who cannot join
- Performance status < 80% (TJU Karnofsky) for patients > or = 60 years old or < 70% for patients < 60.
- HCT-CI Score > 4 points for patients > or = 60 years old or > 5 points for patients < 60.
- HIV positive
- Active involvement of the central nervous system with malignancy
- Inability to obtain informed consent
- Pregnancy
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- Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
- Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > or = 2 ugm/ml
- Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
- Donor Selection All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences. Donor selection will be in compliance with 21 CFR 1271 and TJU BMT Program SOP CP: P009.03.
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies Using Melphalan for T-Cell Tolerization
This is a research study involving the treatment of patients with hematological cancers with allogeneic (cells from a donor) hematopoietic stem cell transplant (HSCT). HSCT is often referred to as bone marrow transplant. Patients who are not expected to have long term survival after conventional therapy will undergo HSCT as a curative therapy after receiving front line therapy for their disease. This project is based on an HSCT approach that has been used at TJU since 2006 with the goal of optimizing this type of treatment further. In this new study, the investigators will substitute the chemotherapy agent, Melphalan (Mel), for cyclophosphamide (CY). Cyclophosphamide was used in the original trial. The research question is whether side effects are less using Mel and if donor T cells can be made tolerant to the recipient with the use of Mel. The proposed study is also more specific in terms of performance status and organ function entry criterion. The investigators observed in the original trial that patients with poor performance upon admission for transplant did not have as good outcomes.
Because many older patients are treated according to this type of transplant, the chemotherapy and radiation used are less intensive than other types of transplant. The name for this in the transplant field is a reduced intensity hematopoietic stem cell transplant. The abbreviations most used in this document are RIC for reduced intensity conditioning, HSCT which refers to the transplant itself, and MEL which refers to the drug, Melphalan.
Read the detailed description
Twenty-nine patients in the Thomas Jefferson University (TJU) Blood and Marrow Transplantation Program have been treated on the research protocol, A Two Step Approach To Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies from HLA Partially-Matched Related Donors (TJU 2 Step RIC, TJU IRB# 06U.328) as of July, 2010. While treatment on this protocol has resulted in durable responses for many older patients and younger, heavily pretreated patients with hematological malignancies, poor performance status at the time of transplant and morbidities related to cyclophosphamide (CY) administration in the regimen have contributed to decreased survival. In addition, disease relapse after hematopoietic stem cell transplantation (HSCT) has been a major cause of mortality for those patients with disease at the time of transplant.
The objective of this research is to improve patient outcomes after treatment on the TJU 2 Step RIC protocol by refining the approach based on outcomes observed in the initial trial. More thorough assessment of performance status prior to HSCT and the substitution of the alkylating agent Melphalan (MEL) for CY to decrease CY-related toxicity while strengthening the anti-leukemic intensity of the regimen for patients with poor-risk disease will be the major strategies used to increase the efficacy of the regimen. MEL has shown efficacy against myeloid malignancies when used in conditioning in RIC HSCT. Patients with AML and MDS were the most common group treated on the initial TJU 2 Step RIC trial and also comprise the largest patient group treated in the TJU Medical Oncology Program.
- Conditions
- Hematologic Malignancies, Acute Leukemia, Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Myeloma
- Being tested
- Fludarabine, Thiotepa, Total Body Irradiation (TBI), Donor Lymphocyte Infusion (DLI), Melphalan
- Keywords
- allogeneic HSCT, Hematopoietic stem cell transplantation
- Medical subject headings
- Hematologic Neoplasms, Myelodysplastic Syndromes, Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms, Plasma Cell, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called fludarabine phosphate, Fludara
Part of the conditioning regimen
ThiotepaDrug
Also called N,N'N'-triethylenethiophosphoramide
Part of the conditioning regimen
Total Body Irradiation (TBI)Radiation
Also called radiotherapy
There is one fraction of total body irradiation (2Gy) as part of the conditioning regimen.
Donor Lymphocyte Infusion (DLI)Biological
Also called buffy coat fusion
Immediately following the conditioning regimen of fludarabine, thiotepa, and TBI, the patient receives a set dose of their donor's T cells (DLI), After the DLI, the donor's T cells will react with the remaining parts of the recipients immune system.
MelphalanDrug
Also called MEL, Melphalan hydrochloride, Alkeran
Two days after the DLI, Melphalan will be given to eliminate the reacting T cells to avoid graft versus host disease. Non-activated T cells should not be affected by the Melphalan and remain to help fight infection.
Hematopoietic stem cell transplantation (HSCT)Device
Also called CliniMACS
One day after the Melphalan ends, the patient will receive their donor's stem cells. This is the actual day of transplant.
The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Transplant Treatment Group | Experimental | All patients treated on this research study. Receives: Drug: Fludarabine; Drug: Thiotepa; Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Melphalan; Device: Hematopoietic stem cell transplantation (HSCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Defined Dose of Melphalan (MEL)
To define the dose of MEL required for the establishment of peripheral T cell tolerance with concomitant immune reconstitution.
Measured: 100 days post-transplant
Phase 2: Non-Relapse Mortality (NRM)
To evaluate the 100 day non-relapse mortality (NRM) rate in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.
Measured: 100 days post-treatment
Secondary outcomes (4)
Relapse Rate
To compare relapse rates in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.
Measured: At 1 and 3 years
GVHD Incidence and Severity
To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen using MEL for T cell tolerization as well as tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.
Measured: At 1 and 3 years
Engraftment Rate and Lymphoid Reconstitution
To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial.
Measured: 100 days post-transplant
Overall Survival
To assess overall survival in patients undergoing HSCT treated on this trial.
Measured: At 1 and 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2011 (estimated)
- Study startApr 2011
- Primary completionMay 2012
- Study completionAug 2012
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dolores Grosso, DNP, CRNP, Principal investigator, Thomas Jefferson UniversityNeal Flomenberg, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01350258
- Sponsor's protocol ID
- 10D.535
- Other IDs
- 2010-40, JT 2173
- Status last verified
- May 2025
- First submitted
- 4 May 2011
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies Using Melphalan for T-Cell Tolerization
- ClinicalTrials.gov ID
- NCT01350258
- Acronym / sponsor ID
- 10D.535
- Conditions
- Hematologic Malignancies, Acute Leukemia, Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Myeloma
- Keywords
- allogeneic HSCT, Hematopoietic stem cell transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- May 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 9 May 2011 (estimated)
- Results
- Posted 24 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study involving the treatment of patients with hematological cancers with allogeneic (cells from a donor) hematopoietic stem cell transplant (HSCT). HSCT is often referred to as bone marrow transplant. Patients who are not expected to have long term survival after conventional therapy will undergo HSCT as a curative therapy after receiving front line therapy for their disease. This project is based on an HSCT approach that has been used at TJU since 2006 with the goal of optimizing this type of treatment further. In this new study, the investigators will substitute the chemotherapy agent, Melphalan (Mel), for cyclophosphamide (CY). Cyclophosphamide was used in the original trial. The research question is whether side effects are less using Mel and if donor T cells can be made tolerant to the recipient with the use of Mel. The proposed study is also more specific in terms of performance status and organ function entry criterion. The investigators observed in the original trial that patients with poor performance upon admission for transplant did not have as good outcomes.
Because many older patients are treated according to this type of transplant, the chemotherapy and radiation used are less intensive than other types of transplant. The name for this in the transplant field is a reduced intensity hematopoietic stem cell transplant. The abbreviations most used in this document are RIC for reduced intensity conditioning, HSCT which refers to the transplant itself, and MEL which refers to the drug, Melphalan.
Detailed description
Twenty-nine patients in the Thomas Jefferson University (TJU) Blood and Marrow Transplantation Program have been treated on the research protocol, A Two Step Approach To Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies from HLA Partially-Matched Related Donors (TJU 2 Step RIC, TJU IRB# 06U.328) as of July, 2010. While treatment on this protocol has resulted in durable responses for many older patients and younger, heavily pretreated patients with hematological malignancies, poor performance status at the time of transplant and morbidities related to cyclophosphamide (CY) administration in the regimen have contributed to decreased survival. In addition, disease relapse after hematopoietic stem cell transplantation (HSCT) has been a major cause of mortality for those patients with disease at the time of transplant.
The objective of this research is to improve patient outcomes after treatment on the TJU 2 Step RIC protocol by refining the approach based on outcomes observed in the initial trial. More thorough assessment of performance status prior to HSCT and the substitution of the alkylating agent Melphalan (MEL) for CY to decrease CY-related toxicity while strengthening the anti-leukemic intensity of the regimen for patients with poor-risk disease will be the major strategies used to increase the efficacy of the regimen. MEL has shown efficacy against myeloid malignancies when used in conditioning in RIC HSCT. Patients with AML and MDS were the most common group treated on the initial TJU 2 Step RIC trial and also comprise the largest patient group treated in the TJU Medical Oncology Program.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant Treatment Group | Experimental | Drug: Fludarabine, Drug: Thiotepa, Radiation: Total Body Irradiation (TBI), Biological: Donor Lymphocyte Infusion (DLI), Drug: Melphalan, Device: Hematopoietic stem cell transplantation (HSCT)All patients treated on this research study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as:
- Patients must have a related donor who is at least a 4 antigen match at the HLA-A; B; C; DR loci.
- Patients must adequate organ function:
- Performance status > or = 80% (TJU Karnofsky) for patients > or = 60 years old or > or = 70% for patients < 60.
- HCT-CI Score < or = 4 points for patients > or = 60 years old or < or = 5 points for patients < 60.
Key exclusion criteria (10 listed)
- Performance status < 80% (TJU Karnofsky) for patients > or = 60 years old or < 70% for patients < 60.
- HCT-CI Score > 4 points for patients > or = 60 years old or > 5 points for patients < 60.
- HIV positive
- Active involvement of the central nervous system with malignancy
- Inability to obtain informed consent
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 |
|---|---|---|
| FludarabineAlso: fludarabine phosphate, FludaraPart of the conditioning regimen | Drug | Transplant Treatment Group |
| ThiotepaAlso: N,N'N'-triethylenethiophosphoramidePart of the conditioning regimen | Drug | Transplant Treatment Group |
| Total Body Irradiation (TBI)Also: radiotherapyThere is one fraction of total body irradiation (2Gy) as part of the conditioning regimen. | Radiation | Transplant Treatment Group |
| Donor Lymphocyte Infusion (DLI)Also: buffy coat fusionImmediately following the conditioning regimen of fludarabine, thiotepa, and TBI, the patient receives a set dose of their donor's T cells (DLI), After the DLI, the donor's T cells will react with the remaining parts of the recipients immune system. | Biological | Transplant Treatment Group |
| MelphalanAlso: MEL, Melphalan hydrochloride, AlkeranTwo days after the DLI, Melphalan will be given to eliminate the reacting T cells to avoid graft versus host disease. Non-activated T cells should not be affected by the Melphalan and remain to help fight infection. | Drug | Transplant Treatment Group |
| Hematopoietic stem cell transplantation (HSCT)Also: CliniMACSOne day after the Melphalan ends, the patient will receive their donor's stem cells. This is the actual day of transplant. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation. | Device | Transplant Treatment Group |
Primary outcome
Phase 1: Defined Dose of Melphalan (MEL)
Time frame: 100 days post-transplant
To define the dose of MEL required for the establishment of peripheral T cell tolerance with concomitant immune reconstitution.
Phase 2: Non-Relapse Mortality (NRM)
Time frame: 100 days post-treatment
To evaluate the 100 day non-relapse mortality (NRM) rate in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.
4 secondary outcomes
Relapse Rate
Time frame: At 1 and 3 years
GVHD Incidence and Severity
Time frame: At 1 and 3 years
Engraftment Rate and Lymphoid Reconstitution
Time frame: 100 days post-transplant
Overall Survival
Time frame: At 1 and 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer CenterLink provided by the sponsor.
- Thomas Jefferson University HospitalsLink provided by the sponsor.
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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.
Dolores Grosso, DNP, CRNP principal investigator
Thomas Jefferson University
Neal Flomenberg, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fludarabine, Thiotepa and Total Body Irradiation (TBI) in people with Hematologic Malignancies and Acute Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
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 16 inclusion and 10 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 31 May 2025. 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 United States. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 24 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase 1: Defined Dose of Melphalan (MEL) (time frame: 100 days post-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 31 May 2025.