Hematologic MalignancyPhase 2NCT01341301
Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies
A Phase 2 study testing Total Body Irradiation, Donor Lymphocyte Infusion (DLI) and Cyclophosphamide in people with Hematologic Malignancy, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial summary
The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- Total Body Irradiation, Donor Lymphocyte Infusion (DLI) and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to 7 Aug 2014
- Phase
- Phase 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 hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR).
- Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
- Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci.
- Patients must adequate organ function:
- Left ventricular ejection fraction (LVEF) of >50 %
- Diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) >50 % of predicted
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- Adequate liver function as defined by a serum bilirubin <1.8, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times upper limit of normal
- Creatinine clearance of > 60 ml/min
- Karnofsky Performance Status of > 80% on the modified KPS tool
- Patients must be willing to use contraception if they have childbearing potential.
- Able to give informed consent
Who cannot join
- Modified Karnofsky performance status (KPS) of <80%
- > 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index
- Untreated class I or II antibodies against donor HLA antigens
- HIV positive
- Active involvement of the central nervous system with malignancy
- Psychiatric disorder that would preclude patients from signing an informed consent
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- Pregnancy, or unwillingness to use contraception if they have child bearing potential
- Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder
- Alemtuzumab treatment within 8 weeks of HSCT admission.
- Anti-thymocyte globulin (ATG) level of > 2 ugm/ml
- Patients with active inflammatory processes including Tmax >101 or active tissue inflammation are excluded
- Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Human Leukocyte Antigen Partially-Matched Related Donor
The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.
Read the detailed description
This is a phase II study in which patients receive a haploidentical HSCT from a single donor. The period between the donor lymphocyte infusion (DLI) and tolerizing doses of CY has been extended to allow for an increased period of allogeneic response against tumor targets. The outcomes of patients undergoing this extra time period will be compared to historical data to assess efficacy.
Primary Objective:
- To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with an extra day inserted between the DLI and administration of cyclophosphamide (CY).
Secondary Objectives:
- To assess the consistency and pace of engraftment.
- To assess the pace of T cell and B cell immune recovery.
- To assess regimen related toxicity, (GVHD) graft-versus-host disease incidence and severity, and overall survival in patients undergoing treatment on this protocol. .
- To assess the tolerance of the period of fever, diarrhea, and rash in each arm in an effort to determine whether a longer interval prior to cytoxan changes this side effect qualitatively compared to prior patient groups or concurrent patient groups. N.B. Patients with hematologic malignancies in remission will continue to be transplanted without modification to the original 2-step approach and will serve as a concurrent comparison group.
- To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens.
- To determine the number of cluster of differentiation 4 (CD4+) cluster of differentiation 25 (CD25+) FOXP3+ regulatory cells post HSCT and to assess whether this is correlated with the development of GVHD after transplant.
- Conditions
- Hematologic Malignancy
- Being tested
- Total Body Irradiation, Donor Lymphocyte Infusion (DLI), Cyclophosphamide, Tacrolimus, Mycophenolate mofetil
- Keywords
- allogeneic stem cell transplant, TJU 2 Step, HSCT, Hematopoietic stem cell transplantation
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Body IrradiationRadiation
Also called TBI
Undergo TBI
Donor Lymphocyte Infusion (DLI)Biological
Also called DLI
Undergo DLI
CyclophosphamideDrug
Also called Cytoxan, Endoxan, Endoxana, Enduxan
Given IV
TacrolimusDrug
Also called Advagraf, Prograf, Protopic
Given IV or PO
Also called Cellcept
Given IV or PO
Allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo allogeneic HSCT
Laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic HSCT | Experimental | CONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0
GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. Receives: Radiation: Total Body Irradiation; Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Procedure: Allogeneic hematopoietic stem cell transplantation; Other: Laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)
To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.
Measured: 1 year after undergoing hematopoietic stem cell transplant
Secondary outcomes (3)
Pace of T-cell and B-cell Immune Recovery
Reported descriptively
Measured: Assessed up to 1 year
Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0
Reported descriptively
Measured: Assessed up to 1 year
Incidence and Severity of GVHD, Graded According to Standard Criteria
Reported descriptively
Measured: Assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2011 (estimated)
- Study startMay 2010
- Primary completion4 Nov 2013
- Study completion7 Aug 2014
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 MalignancyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 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
- Neal Flomenberg, MD, Principal investigator, Thomas Jefferson UniversityDolores Grosso, DNP, CRNP, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01341301
- Sponsor's protocol ID
- 10D.06
- Other IDs
- 2009-41, JT 1521
- Status last verified
- Apr 2025
- First submitted
- 21 Apr 2011
- Last updated
- 30 Apr 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 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies Using One Human Leukocyte Antigen Partially-Matched Related Donor
- ClinicalTrials.gov ID
- NCT01341301
- Acronym / sponsor ID
- 10D.06
- Conditions
- Hematologic Malignancy
- Keywords
- allogeneic stem cell transplant, TJU 2 Step, HSCT, Hematopoietic stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- 4 Nov 2013 (actual)
- Study completion
- 7 Aug 2014 (actual)
- First posted
- 25 Apr 2011 (estimated)
- Results
- Posted 16 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to examine the survival of patients undergoing partially matched hematopoietic stem cell transplant (HSCT) on a new type of treatment approach, which has been developed specifically for patients who have evidence of their disease at the time of transplant. In this research study, a way of strengthening the response of the donor cells against the disease has been developed. Patients will undergo one additional day between the two steps of the transplant which may allow their donor's cells to fight the disease more effectively.
Detailed description
This is a phase II study in which patients receive a haploidentical HSCT from a single donor. The period between the donor lymphocyte infusion (DLI) and tolerizing doses of CY has been extended to allow for an increased period of allogeneic response against tumor targets. The outcomes of patients undergoing this extra time period will be compared to historical data to assess efficacy.
Primary Objective:
- To assess 1 year relapse free survival in patients undergoing hematopoietic stem cell transplant (HSCT) using the Thomas Jefferson University (TJU) 2 step approach with an extra day inserted between the DLI and administration of cyclophosphamide (CY).
Secondary Objectives:
- To assess the consistency and pace of engraftment.
- To assess the pace of T cell and B cell immune recovery.
- To assess regimen related toxicity, (GVHD) graft-versus-host disease incidence and severity, and overall survival in patients undergoing treatment on this protocol. .
- To assess the tolerance of the period of fever, diarrhea, and rash in each arm in an effort to determine whether a longer interval prior to cytoxan changes this side effect qualitatively compared to prior patient groups or concurrent patient groups. N.B. Patients with hematologic malignancies in remission will continue to be transplanted without modification to the original 2-step approach and will serve as a concurrent comparison group.
- To collect leukemia samples prior to transplant and after relapse whenever possible. To assess the overall degree of HLA-class I and class II expression on these paired samples. To test for loss of one or both HLA haplotypes in the relapsed tumor specimens.
- To determine the number of cluster of differentiation 4 (CD4+) cluster of differentiation 25 (CD25+) FOXP3+ regulatory cells post HSCT and to assess whether this is correlated with the development of GVHD after transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic HSCT | Experimental | Radiation: Total Body Irradiation, Biological: Donor Lymphocyte Infusion (DLI), Drug: Cyclophosphamide, Drug: Tacrolimus, Drug: Mycophenolate mofetil, Procedure: Allogeneic hematopoietic stem cell transplantation, Other: Laboratory biomarker analysisCONDITIONING: Patients undergo Total Body Irradiation (TBI) twice daily (BID) on days -10 to -7. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients receive DLI on day -6 and undergo cluster of differentiation 34 (CD34+) selected allogeneic HSCT on day 0 GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO on days -1 with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID or PO on days -1 to 28. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater complete remission (CR).
- Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (ie <5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
- Patients must have at least one related donor who is HLA mismatched in the GVHD direction at two or more HLA loci.
- Patients must adequate organ function:
- Karnofsky Performance Status of > 80% on the modified KPS tool
Key exclusion criteria (12 listed)
- Modified Karnofsky performance status (KPS) of <80%
- > 5 Comorbidity Points on the hematopoietic cell transplantation comorbidity index (HCT-CI) Index
- Untreated class I or II antibodies against donor HLA antigens
- HIV positive
- Active involvement of the central nervous system with malignancy
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 |
|---|---|---|
| Total Body IrradiationAlso: TBIUndergo TBI | Radiation | Allogeneic HSCT |
| Donor Lymphocyte Infusion (DLI)Also: DLIUndergo DLI | Biological | Allogeneic HSCT |
| CyclophosphamideAlso: Cytoxan, Endoxan, Endoxana, EnduxanGiven IV | Drug | Allogeneic HSCT |
| TacrolimusAlso: Advagraf, Prograf, ProtopicGiven IV or PO | Drug | Allogeneic HSCT |
| Mycophenolate mofetilAlso: CellceptGiven IV or PO | Drug | Allogeneic HSCT |
| Allogeneic hematopoietic stem cell transplantationUndergo allogeneic HSCT | Procedure or surgery | Allogeneic HSCT |
| Laboratory biomarker analysisCorrelative studies | Other | Allogeneic HSCT |
Primary outcome
Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT)
Time frame: 1 year after undergoing hematopoietic stem cell transplant
To assess relapse free survival in participants undergoing Hematopoietic Stem Cell Transplant (HSCT) using the Thomas Jefferson University 2 step approach with an extra day inserted between the donor lymphocyte infusion (DLI) and administration of cyclophosphamide.
3 secondary outcomes
Pace of T-cell and B-cell Immune Recovery
Time frame: Assessed up to 1 year
Regimen Related Toxicities Graded According to the National Cancer Institute (NCI) Common Toxicity Criteria, Version 3.0
Time frame: Assessed up to 1 year
Incidence and Severity of GVHD, Graded According to Standard Criteria
Time frame: Assessed up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 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.
Neal Flomenberg, MD principal investigator
Thomas Jefferson University
Dolores Grosso, DNP, CRNP 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 2 study testing Total Body Irradiation, Donor Lymphocyte Infusion (DLI) and Cyclophosphamide in people with Hematologic Malignancy, 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 11 inclusion and 12 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: finished, as of the sponsor's last update on 30 Apr 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 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?
Yes. Results are posted in the registry (first posted 16 Mar 2018). 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?
Number of Participants That Experience One Year Relapse Free Survival After Undergoing Hematopoietic Stem Cell Transplant (HSCT) (time frame: 1 year after undergoing hematopoietic stem cell transplant). 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 30 Apr 2025.