Acute Myeloid LeukemiaPhase 1NCT00697684
Reduced Intensity Conditioning With Clofarabine, Antithymocyte Globulin (ATG), Total Lymphoid Irradiation (TLI) Followed by Allogeneic Stem Cell Transplant
A Phase 1 study testing Antithymocyte Globulin and Clofarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Beth Israel Deaconess Medical Center at 2 sites in United States.
Trial summary
This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the presence of the circulating regulatory as compared to activated T cell populations will be assessed.The recovery of DC populations… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia
- What is being tested?
- Antithymocyte Globulin and Clofarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2008to Nov 2023
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a)acute myeloid leukemia exclusive of patients in first complete remission with good risk cytogenetics (translocation 8,21,translocation 15, 17 or inversion 16); B)myelodysplastic syndrome; c)acute lymphocytic leukemia exclusive of patients in first remission without negative prognostic markers; d) relapsed or refractory nonHodgkin's lymphoma or Hodgkin's disease; e)relapsed or refractory multiple myeloma or f)relapsed or refractory chronic lymphocytic leukemia.
- Patients who are considered appropriate for reduced intensity transplantation must present with at least one of the following: A. Age over 50 B. History of a prior hematopoietic stem cell transplant C. Patient with compromised organ function or comorbid conditioning such that a standard ablative transplant would be considered high risk. D. Patient with low grade Lymphoma or CLL for which reduced intensity transplant would be the optimal therapy compared to an ablative regimen
- Patients will have a related or unrelated donor matched at 5/6 or 6/6 HLA loci.
- Patients must be greater than or equal to 18 years old, and younger than or equal to 75 years old to participate in the study.
- Patients must have ECOG performance status of 0-2
- Pulmonary function tests demonstrate DLCO (adjusted for Hgb)>50% predicted
Show all 15Show fewer
- Cardiac ejection fraction >40%
- Laboratories:
- Bilirubin less than or equal to 1.5mg/dL x ULN
- AST/ALT/Alkaline Phosphatase less than or equal to 2.5x ULN
- Serum creatinine less than or equal to 1.0mg/dL; if serum creatinine > 1.0MG/dL, then the estimated glomerular filtration rate (GFR) must be >60mL/min/1.73m^2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GRF (ml/min/1.73m^2)=186x (serum creatinine)^1.154x(age in years)^-0.203x(0.742 if patient is female) x (1.212 if patient is black)
- Patients with serologic evidence of hepatitis B or C exposure will undergo liver biopsy to assess for presence of active hepatitis or fibrosis and quantification of risk of proceeding with transplant.
- 10. All patients must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. All patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines.
- 11. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
- 12. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
Who cannot join
- Patients who are HIV+ will be excluded.
- Patients must not have serious intercurrent illness such as uncontrolled systemic infection or significant organ compromise which significantly increases the risk of undergoing allogeneic transplantation.
- Pregnant and lactating women will be excluded.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Reduced Intensity Conditioning With Clofarabine Antithymocyte Globulin and Total Lymphoid Irradiation Followed by Allogeneic Hematopoietic Stem Cell Transplantation
This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the presence of the circulating regulatory as compared to activated T cell populations will be assessed.The recovery of DC populations post-transplant will be examined, along with the effect of the regimen on disease free and overall survival.
Read the detailed description
One approach to limit the toxicity of allogeneic transplantation has been the use of nonmyeloablative regimens preceding the infusion of allogeneic cells.In this strategy, patients receive immunosuppressive therapy that allows for the engraftment of donor cells without the immediate eradication of patient hematopoiesis.The primary mechanism by which the underlying disease is eradicated is not through chemotherapy mediated cytoreduction, but rather through the donor lymphocyte mediated graft versus tumor effect.As a result, patients experience far less regimen related toxicity.Therefore, the adoption of this strategy may allow for the use of allogeneic transplantation in disease settings and patient populations for which it had not been readily applicable in the past.
Over the past several years, the use nonmyeloablative transplant has rapidly expanded.Several reduced intensity conditioning regimens have been developed including fludarabine and cyclophosphamide; fludarabine and melphalan; fludarabine, ATG and low dose busulfan; and fludarabine and low dose TBI. Investigators have demonstrated the feasibility of this treatment approach with the majority of patients demonstrating donor engraftment,decreased regimen related toxicity, and graft mediated regression of disease.In some studies, patients demonstrate a period of mixed donor/host chimerism in which the infusion of donor lymphocytes is associated with achievement of complete donor chimerism.
Although regimen related toxicity is decreased following reduced intensive conditioning regimens, graft versus host disease and opportunistic infections remain a significant source of morbidity and mortality following nonmyeloablative allogeneic transplantation. The impact of nonmyeloablative transplantation on immunological reconstitution has not been fully defined. Persistence of host antigen presenting cells in the post-transplant period may increase the incidence of GVHD due to the presentation of alloantigens to donor T cells. In contrast, residual host cellular immunity may provide enhanced protection against infectious pathogens and allow for more rapid education of donor lymphocytes.
The use of clofarabine in place of fludarabine in combination with cyclophosphamide may augment the anti-leukemia effect of the regimen, enhance cytoreduction, and increase the efficacy of reduced intensity allogeneic transplantation in this setting.A potential issue associated with the use of clofarabine and cyclophosphamide as pre-transplant conditioning is whether the regimen would be sufficiently immunosuppressive to reliably facilitate engraftment of donor hematopoiesis.Another concern relates to the significant incidence of graft versus host disease which remains a major source of morbidity and mortality following reduced intensity transplantation.The use of TLI and ATG has been studied in the context of allogeneic transplantation and has been shown to effectively support engraftment in animal models and clinical trials.TLI has been shown to promote immune tolerance resulting in a decrease in the incidence of graft versus host disease (GVHD).It has been shown to decrease the incidence of rejection following transplantation of a T cell depleted allograft.The conditioning regimen of TLI and cyclophosphamide results in successful engraftment in patients with aplastic anemia.
Regulatory T cells represent a population of T lymphocytes that demonstrate an immunosuppressive phenotype and play an important role in the prevention of autoimmunity and transplant rejection.Regulatory cells express the inhibitory cytokines IL-10 and TGFβ and are thought to suppress immune activation through direct cell contact.Similar to activated effector cells they coexpress CD4 and CD25.Regulatory T cells may be identified by the high levels of CD25 expression and the presence of CTLA-4 and FOXP3.Regulatory T cells demonstrate minimal proliferation to allogeneic stimuli and inhibit third party mixed lymphocyte responses. Increased presence of regulatory T cells have been found in the tumor bed, draining lymph nodes, and circulation in patients with malignancy and inhibit host anti-tumor immune responses.
There has been increasing interest in evaluating the role of regulatory T cells as a means of inhibiting graft versus host disease. In animal models, selective introduction of regulatory T cells prevents the development of graft versus host disease without compromising immune reconstitution or anti-tumor immunity. A variety of strategies for the ex vivo expansion and isolation of regulatory T cells have been explored. A limiting factor has been the similar patterns of expression of cell surface markers between regulatory and activated T cell populations. iNKT cells represent another population of immunomodulatory cells thought to be essential for the generation of tolerance.In pre-clinical models, TLI has been shown to modulate immune effector cells resulting in increased levels of circulating regulatory T cells, preventing GVHD in a mismatched transplant setting.It is thought that iNKT cells are selectively preserved after TLI which polarize T cells towards an inhibitory phenotype. In a clinical study, 37 patients with lymphoid malignancies or acute leukemia underwent conditioning with TLI administered as 10 fractions of 80cGy and ATG.Only 2 patients developed acute GVHD despite the observation of a graft versus disease effect.Of note, a significant increase in the number of donor CD4+ T cells expressing IL-4 was observed suggesting that the immune modulation resulting from TLI/ATG polarized cells towards a TH-2 phenotype.As such, TLI/ATG would like facilitate engraftment and decrease the incidence of GVHD in patients undergoing conditioning with clofarabine.Most importantly, by modulating the host immune effectors but not depleting donor T cells, this strategy should not significantly inhibit the graft versus tumor effect.The prevalence of dendritic cell (DC) subsets (DC1 vs. DC2) in the hematopoietic graft have also been shown to effect the risk of GVHD.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia, Relapsed/Refractory Chronic Lymphocytic Leukemia, Relapsed/Refractory Non Hodgkin's Lymphoma, Hodgkins Disease
- Being tested
- Antithymocyte Globulin, Clofarabine
- Keywords
- Reduced Intensity Allogeneic Stem Cell Transplant, Clofarabine, Rabbit Antithymocyte Globulin, Total Lymphoid Radiation
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithymocyte GlobulinDrug
ClofarabineDrug
Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
ClofarabineDrug
Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
ClofarabineDrug
Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | No intervention | Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). |
| Cohort 2 | Experimental | Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). Receives: Drug: Antithymocyte Globulin; Drug: Clofarabine |
| Cohort 3 | Experimental | Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). Receives: Drug: Antithymocyte Globulin; Drug: Clofarabine |
| Cohort 4 | Experimental | Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). Receives: Drug: Antithymocyte Globulin; Drug: Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the toxicity and donor engraftment following treatment with a reduced intensity preparative regimen consisting of clofarabine, rabbit antithymocyte globulin (ATG), and total lymphoid irradiation followed by the infusion of allogeneic stem cells
Measured: 30 days
Secondary outcomes (3)
To determine the incidence of acute and chronic graft versus host disease following clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation.
Measured: 1 year
2. To evaluate the nature of immunologic reconstitution in patients treated clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation. The impact of the regimen on the phenotypic and functional characteristics of dendritic cell
Measured: 1 year
To determine the disease free survival and overall survival of patients undergoing allogeneic transplantation following following clofarabine, rabbit ATG, and total lymphoid irradiation.
Measured: Patient lifetime
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2020
- Study completionNov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Principal investigator, David Avigan, Beth Israel Deaconess Medical Center
- Investigators
- David E Avigan, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00697684
- Sponsor's protocol ID
- 07-384
- Status last verified
- Nov 2023
- First submitted
- 12 Jun 2008
- Last updated
- 28 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Reduced Intensity Conditioning With Clofarabine Antithymocyte Globulin and Total Lymphoid Irradiation Followed by Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00697684
- Acronym / sponsor ID
- 07-384
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphocytic Leukemia, Relapsed/Refractory Chronic Lymphocytic Leukemia, Relapsed/Refractory Non Hodgkin's Lymphoma, Hodgkins Disease
- Keywords
- Reduced Intensity Allogeneic Stem Cell Transplant, Clofarabine, Rabbit Antithymocyte Globulin, Total Lymphoid Radiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Jun 2008
- Primary completion
- Dec 2020 (actual)
- Study completion
- Nov 2023 (actual)
- First posted
- 16 Jun 2008 (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.
This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the presence of the circulating regulatory as compared to activated T cell populations will be assessed.The recovery of DC populations post-transplant will be examined, along with the effect of the regimen on disease free and overall survival.
Detailed description
One approach to limit the toxicity of allogeneic transplantation has been the use of nonmyeloablative regimens preceding the infusion of allogeneic cells.In this strategy, patients receive immunosuppressive therapy that allows for the engraftment of donor cells without the immediate eradication of patient hematopoiesis.The primary mechanism by which the underlying disease is eradicated is not through chemotherapy mediated cytoreduction, but rather through the donor lymphocyte mediated graft versus tumor effect.As a result, patients experience far less regimen related toxicity.Therefore, the adoption of this strategy may allow for the use of allogeneic transplantation in disease settings and patient populations for which it had not been readily applicable in the past.
Over the past several years, the use nonmyeloablative transplant has rapidly expanded.Several reduced intensity conditioning regimens have been developed including fludarabine and cyclophosphamide; fludarabine and melphalan; fludarabine, ATG and low dose busulfan; and fludarabine and low dose TBI. Investigators have demonstrated the feasibility of this treatment approach with the majority of patients demonstrating donor engraftment,decreased regimen related toxicity, and graft mediated regression of disease.In some studies, patients demonstrate a period of mixed donor/host chimerism in which the infusion of donor lymphocytes is associated with achievement of complete donor chimerism.
Although regimen related toxicity is decreased following reduced intensive conditioning regimens, graft versus host disease and opportunistic infections remain a significant source of morbidity and mortality following nonmyeloablative allogeneic transplantation. The impact of nonmyeloablative transplantation on immunological reconstitution has not been fully defined. Persistence of host antigen presenting cells in the post-transplant period may increase the incidence of GVHD due to the presentation of alloantigens to donor T cells. In contrast, residual host cellular immunity may provide enhanced protection against infectious pathogens and allow for more rapid education of donor lymphocytes.
The use of clofarabine in place of fludarabine in combination with cyclophosphamide may augment the anti-leukemia effect of the regimen, enhance cytoreduction, and increase the efficacy of reduced intensity allogeneic transplantation in this setting.A potential issue associated with the use of clofarabine and cyclophosphamide as pre-transplant conditioning is whether the regimen would be sufficiently immunosuppressive to reliably facilitate engraftment of donor hematopoiesis.Another concern relates to the significant incidence of graft versus host disease which remains a major source of morbidity and mortality following reduced intensity transplantation.The use of TLI and ATG has been studied in the context of allogeneic transplantation and has been shown to effectively support engraftment in animal models and clinical trials.TLI has been shown to promote immune tolerance resulting in a decrease in the incidence of graft versus host disease (GVHD).It has been shown to decrease the incidence of rejection following transplantation of a T cell depleted allograft.The conditioning regimen of TLI and cyclophosphamide results in successful engraftment in patients with aplastic anemia.
Regulatory T cells represent a population of T lymphocytes that demonstrate an immunosuppressive phenotype and play an important role in the prevention of autoimmunity and transplant rejection.Regulatory cells express the inhibitory cytokines IL-10 and TGFβ and are thought to suppress immune activation through direct cell contact.Similar to activated effector cells they coexpress CD4 and CD25.Regulatory T cells may be identified by the high levels of CD25 expression and the presence of CTLA-4 and FOXP3.Regulatory T cells demonstrate minimal proliferation to allogeneic stimuli and inhibit third party mixed lymphocyte responses. Increased presence of regulatory T cells have been found in the tumor bed, draining lymph nodes, and circulation in patients with malignancy and inhibit host anti-tumor immune responses.
There has been increasing interest in evaluating the role of regulatory T cells as a means of inhibiting graft versus host disease. In animal models, selective introduction of regulatory T cells prevents the development of graft versus host disease without compromising immune reconstitution or anti-tumor immunity. A variety of strategies for the ex vivo expansion and isolation of regulatory T cells have been explored. A limiting factor has been the similar patterns of expression of cell surface markers between regulatory and activated T cell populations. iNKT cells represent another population of immunomodulatory cells thought to be essential for the generation of tolerance.In pre-clinical models, TLI has been shown to modulate immune effector cells resulting in increased levels of circulating regulatory T cells, preventing GVHD in a mismatched transplant setting.It is thought that iNKT cells are selectively preserved after TLI which polarize T cells towards an inhibitory phenotype. In a clinical study, 37 patients with lymphoid malignancies or acute leukemia underwent conditioning with TLI administered as 10 fractions of 80cGy and ATG.Only 2 patients developed acute GVHD despite the observation of a graft versus disease effect.Of note, a significant increase in the number of donor CD4+ T cells expressing IL-4 was observed suggesting that the immune modulation resulting from TLI/ATG polarized cells towards a TH-2 phenotype.As such, TLI/ATG would like facilitate engraftment and decrease the incidence of GVHD in patients undergoing conditioning with clofarabine.Most importantly, by modulating the host immune effectors but not depleting donor T cells, this strategy should not significantly inhibit the graft versus tumor effect.The prevalence of dendritic cell (DC) subsets (DC1 vs. DC2) in the hematopoietic graft have also been shown to effect the risk of GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | No intervention | –Transplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). |
| Cohort 2 | Experimental | Drug: Antithymocyte Globulin, Drug: ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). |
| Cohort 3 | Experimental | Drug: Antithymocyte Globulin, Drug: ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). |
| Cohort 4 | Experimental | Drug: Antithymocyte Globulin, Drug: ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with a)acute myeloid leukemia exclusive of patients in first complete remission with good risk cytogenetics (translocation 8,21,translocation 15, 17 or inversion 16); B)myelodysplastic syndrome; c)acute lymphocytic leukemia exclusive of patients in first remission without negative prognostic markers; d) relapsed or refractory nonHodgkin's lymphoma or Hodgkin's disease; e)relapsed or refractory multiple myeloma or f)relapsed or refractory chronic lymphocytic leukemia.
- Patients who are considered appropriate for reduced intensity transplantation must present with at least one of the following: A. Age over 50 B. History of a prior hematopoietic stem cell transplant C. Patient with compromised organ function or comorbid conditioning such that a standard ablative transplant would be considered high risk. D. Patient with low grade Lymphoma or CLL for which reduced intensity transplant would be the optimal therapy compared to an ablative regimen
- Patients will have a related or unrelated donor matched at 5/6 or 6/6 HLA loci.
- Patients must be greater than or equal to 18 years old, and younger than or equal to 75 years old to participate in the study.
- Patients must have ECOG performance status of 0-2
Key exclusion criteria (3 listed)
- Patients who are HIV+ will be excluded.
- Patients must not have serious intercurrent illness such as uncontrolled systemic infection or significant organ compromise which significantly increases the risk of undergoing allogeneic transplantation.
- Pregnant and lactating women will be excluded.
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 |
|---|---|---|
| Antithymocyte Globulin | Drug | Cohort 2, Cohort 3, Cohort 4 |
| ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 20mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 100 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). | Drug | Cohort 2, Cohort 3, Cohort 4 |
| ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 30mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 150 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). | Drug | Cohort 2, Cohort 3, Cohort 4 |
| ClofarabineTransplant conditioning will begin day -11 with 5 days of TLI at a dose of 80 cGy per day administered in conjunction with rabbit ATG at a dose of 1.5 mg/kg per day (day -11 to -7). Clofarabine will be given at 40mg/m2/d IV infused over 1 hour x 5 days (day -6 to -2), for a total dose of 200 mg/m(2). TLI will be completed at 80 cGy per day (day -4 to 0) for a total of 10 fractions (800 cGy). | Drug | Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
To assess the toxicity and donor engraftment following treatment with a reduced intensity preparative regimen consisting of clofarabine, rabbit antithymocyte globulin (ATG), and total lymphoid irradiation followed by the infusion of allogeneic stem cells
Time frame: 30 days
3 secondary outcomes
To determine the incidence of acute and chronic graft versus host disease following clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation.
Time frame: 1 year
2. To evaluate the nature of immunologic reconstitution in patients treated clofarabine, rabbit ATG, total lymphoid irradiation, and allogeneic transplantation. The impact of the regimen on the phenotypic and functional characteristics of dendritic cell
Time frame: 1 year
To determine the disease free survival and overall survival of patients undergoing allogeneic transplantation following following clofarabine, rabbit ATG, and total lymphoid irradiation.
Time frame: Patient lifetime
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
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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.
David E Avigan, MD principal investigator
Beth Israel Deaconess Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antithymocyte Globulin and Clofarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Beth Israel Deaconess Medical Center at 2 sites 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 15 inclusion and 3 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 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the toxicity and donor engraftment following treatment with a reduced intensity preparative regimen consisting of clofarabine, rabbit antithymocyte globulin (ATG), and total lymphoid irradiation followed by the infusion of allogeneic stem cells (time frame: 30 days). 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 28 Nov 2023.