A Phase 2 interventional study of rituximab and busulfan in Chronic Myeloproliferative Disorders, Leukemia and Lymphoma, sponsored by Barbara Ann Karmanos Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-28.
Sponsored by Barbara Ann Karmanos Cancer Institute · Phase 2, Interventional, and Supportive care
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood 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 tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.
OBJECTIVES:
Primary
Secondary
OUTLINE:
Conditioning regimen: Patients receive 1 of 6 conditioning regimens (standard of care treatment) between days -9 and -3, based on diagnosis and the treating physician's preference regarding regimen intensity.
Blood samples are obtained at baseline and periodically during study for correlative biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution, T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after transplantation, and regulatory T-cell reconstitution.
After completion of study therapy, patients are followed periodically for up to 2 years.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 48 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Barbara Ann Karmanos Cancer Institute is the lead sponsor of 158 studies on the registry; 19 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 6 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Diagnosis of a hematological malignancy, including any of the following:
Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting either of the following criteria:
Not in CR and meets the following criteria:
Myelofibrosis or other myeloproliferative disorders meeting the following criteria:
Scheduled to undergo peripheral blood stem cell transplantation from a suitable HLA-matched or -mismatched unrelated donor, as determined by treating physician
PATIENT CHARACTERISTICS:
FVC, FEV_1, or DLCO > 50% predicted
PRIOR CONCURRENT THERAPY:
Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.
Biological: rituximab · Drug: busulfan · Drug: carmustine · Drug: cyclophosphamide · Drug: cytarabine · Drug: etoposide · Drug: fludarabine phosphate · Drug: melphalan · Radiation: total body irradiation (TBI) · Drug: anti-thymocyte globulin IV
Given IV
Also known as: Rituxan, MabThera, Zytux
Given IV
Also known as: Busulfex, Myleran
Given IV
Also known as: Bicnu, Gliadel
Given IV
Also known as: Cytoxan, Cytoxan Lyophilized, Neosar
Given IV
Also known as: Depocyt
Given IV
Also known as: Etopophos, Toposar
Given IV
Also known as: Fludara®
Given IV
Also known as: Alkeran
Given once or twice daily
Also known as: radiotherapy
Given IV
Also known as: Thymoglobulin
Incidence of Acute Graft-versus-host Disease (GVHD)
Time frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
Severity of Acute Graft-versus-host Disease (GVHD)
Time frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
Time frame: Within 6 months after PBSCT
Incidence of Chronic GVHD.
Time frame: Within 2 years after PBSCT
Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
Time frame: post transplant, up to 4 weeks
Overall Survival.
Time frame: At 2 years after PBSCT
Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
Time frame: Within 6 months after PBSCT
Karnofsky Performance Status Performance Status
100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Time frame: At 90 days after PBSCT
| Milestone | Conditioning Regimen |
|---|---|
| Started | 48 |
| Completed | 47 |
| Not completed | 1 |
| Withdrew: Refused further treatment | 1 |
| percentage of participants | All Participants |
|---|---|
| Incidence of Acute Graft-versus-host Disease (GVHD) | 44.7 (33.4 to 56.6) |
| % of participants with severe aGVHD | All Participants |
|---|---|
| Severity of Acute Graft-versus-host Disease (GVHD) | 33.3 (19.2 to 51.3) |
| % of participants with a reported SAE | All Participants |
|---|---|
| Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment. | 93.62 (82.46 to 98.66) |
| percentage of participants | All Participants |
|---|---|
| Incidence of Chronic GVHD. | 44.68 (30.17 to 59.88) |
| Days | All Participants |
|---|---|
| Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] ) | 11 (9 to 15) |
| percentage of participants | All Participants |
|---|---|
| Overall Survival. | 57.4 (44.9 to 73.5) |
| percentage of participants | All Participants |
|---|---|
| Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders) | 80.85 (66.74 to 90.85) |
100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
| units on a scale | All Participants |
|---|---|
| Karnofsky Performance Status Performance Status | 80 (60 to 100) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Conditioning Regimen | — | 44/47 (93.6%) | 0/47 (0%) |
| Event | Conditioning Regimen |
|---|---|
| InfectionInfections and infestations | 24/47 |
| HyperglycemiaMetabolism and nutrition disorders | 12/47 |
| LeukocytesBlood and lymphatic system disorders | 12/47 |
| PlateletsInvestigations | 12/47 |
| HemoglobinInvestigations | 11/47 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 11/47 |
| infection, with normal ANCInfections and infestations | 11/47 |
| LymphopeniaBlood and lymphatic system disorders | 11/47 |
| NeutrophilsInvestigations | 11/47 |
| Rash/DesquamationSkin and subcutaneous tissue disorders | 10/47 |
| Age, Continuous(years) | All Participants |
|---|---|
| Median | 53 (20 to 70) |
| Sex: Female, Male(Participants) | All Participants |
|---|---|
| Female | 17 |
| Male | 30 |
| Region of Enrollment(participants) | All Participants |
|---|---|
| United States | 47 |
This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.
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Barbara Ann Karmanos Cancer Institute