A Phase 2 interventional study of rituximab and mycophenolate mofetil in Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission and Adult Acute Myeloid Leukemia in Remission, sponsored by University of Nebraska. Terminated at 1 site in United States. Open to participants aged 19 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-09-06.
Sponsored by University of Nebraska · Phase 2, Interventional, and Treatment
This phase II trial is studying how well rituximab works in preventing acute graft-versus-host disease (GVHD) in patients undergoing a donor stem cell transplant for hematologic cancer. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, rituximab, together with anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil before and after the transplant may stop this from happening
PRIMARY OBJECTIVES:
I. To determine the incidence of grade II-IV acute GVHD at day 100 after matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) when incorporating rituximab in the conditioning regimen.
SECONDARY OBJECTIVES:
I. To determine the day 100 transplant related mortality after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.
II. To determine overall survival (OS) and disease-free survival (DFS) after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.
III. To determine the cumulative incidence of infectious complications at day 100 after matched unrelated donor HCT when incorporating rituximab in the conditioning regimen.
IV. To determine the effect of rituximab addition to the conditioning regimen on recovery of T regulatory (T-reg) cells, and to determine the effect of T-cell, including T-reg, number in the stem cell product and at day 30 on the incidence of grade II-IV acute GVHD (aGVHD) and the cumulative infectious complications at day 100.
V. To determine the effect of rituximab addition to the conditioning regimen on antigen presenting myeloid cell recovery, and to determine the effect of dendritic cell subset DC1, DC2 and myeloid-derived suppressor cells (MDSC), number in the stem cell graft and at day +30 on the incidence of acute GVHD grade II-IV and the cumulative incidence of infectious complications at day 100.
OUTLINE:
CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and total-body irradiation (TBI); targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI.
GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab intravenously (IV) on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then orally (PO) beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60.
TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.
Patients are followed up periodically for 100 days after transplant.
Exclusion Criteria:
CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and TBI; targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab IV on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then PO beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.
Drug: rituximab · Drug: mycophenolate mofetil · Drug: tacrolimus · Drug: anti-thymocyte globulin · Procedure: allogeneic hematopoietic stem cell transplantation · Other: laboratory biomarker analysis · Biological: graft versus host disease prophylaxis/therapy · Drug: cyclophosphamide · Drug: fludarabine phosphate · Drug: busulfan · Radiation: total-body irradiation · Biological: graft-versus-tumor induction therapy · Biological: immunosuppressive therapy
Given IV
Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Given IV or PO
Also known as: Cellcept, MMF
Given IV
Also known as: FK 506, Prograf
Given IV
Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Stem cell transplant
Correlative studies
Undergo graft versus host disease prophylaxis/therapy
Also known as: prophylaxis/therapy, graft versus host disease, prophylaxis/therapy, GVHD
Given PO or IV
Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Given IV
Also known as: 2-F-ara-AMP, Beneflur, Fludara
Given IV
Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon
Undergo TBI
Also known as: TBI
Undergo graft-versus-tumor induction therapy
Also known as: graft versus host disease induction, graft versus tumor induction
Undergo immunosuppressive therapy
Also known as: immunosuppression
Number of Participants With Grades II-IV Acute GVHD
Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.
Time frame: At day 100
Event-free Survival
Estimated using Kaplan-Meier estimator.
Time frame: From the date of transplant with relapse/progression or death as censored events, up to 2 years
Overall Survival
Estimated using Kaplan-Meier estimator.
Time frame: From the date of transplant with death from any cause as a censored event, up to 2 years
Transplant-related Mortality (TRM)
Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease - Reported as a simple percentage.
Time frame: At day 100
| Milestone | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Started | 20 |
| Completed | 18 |
| Not completed | 2 |
| Withdrew: Ineiligible | 2 |
Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.
| Participants | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Number of Participants With Grades II-IV Acute GVHD | 16 |
Estimated using Kaplan-Meier estimator.
| months | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Event-free Survival | 12 (6 to 18) |
Estimated using Kaplan-Meier estimator.
| months | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Overall Survival | 12 (9 to 18) |
Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease - Reported as a simple percentage.
| Participants | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Transplant-related Mortality (TRM) | 0 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Rituximab and Allogeneic HCT Transplant) | 5/20 (25%) | 10/20 (50%) | 16/20 (80%) |
| Event | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| DiarrheaGastrointestinal disorders | 3/20 |
| pneumonitisInfections and infestations | 3/20 |
| sepsisInfections and infestations | 3/20 |
| acute kidney injuryRenal and urinary disorders | 3/20 |
| cystitisInfections and infestations | 3/20 |
| Immune system disorders-otherImmune system disorders | 2/20 |
| vomitingGastrointestinal disorders | 1/20 |
| anorexiaGastrointestinal disorders | 1/20 |
| mucositis oralGastrointestinal disorders | 1/20 |
| ileusGastrointestinal disorders | 1/20 |
| Event | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| HyperglycemiaMetabolism and nutrition disorders | 8/20 |
| HypokalemiaMetabolism and nutrition disorders | 7/20 |
| HyponatremiaMetabolism and nutrition disorders | 5/20 |
| SepsisInfections and infestations | 5/20 |
| HypophosphatemiaMetabolism and nutrition disorders | 4/20 |
| HypoalbuminemiaMetabolism and nutrition disorders | 4/20 |
| Febrile NeutropeniaBlood and lymphatic system disorders | 3/20 |
| AnorexiaMetabolism and nutrition disorders | 3/20 |
| Mucositis - oralGastrointestinal disorders | 3/20 |
| RashInfections and infestations | 2/20 |
| Age, Continuous(years) | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Median | 39 (21 to 52) |
| Sex: Female, Male(Participants) | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| Female | 11 |
| Male | 9 |
| Region of Enrollment(participants) | Treatment (Rituximab and Allogeneic HCT Transplant) |
|---|---|
| United States | 20 |
This study is terminated, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.
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