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New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.
Treatment-related mortality and recurrence of disease account for the majority of treatment failures in allogeneic transplantation for advanced hematologic malignancies. The most commonly utilized conditioning regimens consist of cyclophosphamide and total-body irradiation or busulfan and cyclophosphamide. Other agents such as etoposide or thiotepa are sometimes added to maximize the antileukemic effect. New conditioning regimens are however still needed to maximize efficacy and limit treatment-related deaths. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Active Comparator | All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor. |
|
| Arm 2 | Active Comparator | All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fludarabine/busulfan | Drug | All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Engraftment. | Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant. | Up to 30 days post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Participants With 100 Day Transplant-related Mortality. | Day 100 transplant-related mortality was measured in both groups. | Up to 100 days post-transplant. |
| Time to ANC and Platelet Engraftment |
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Inclusion Criteria:
Patients with the following diseases:
Age 10-65 years.
Zubrod performance status less than or equal to 2.
Adequate cardiac and pulmonary function. Patients with decreased LVEF < 40% or DLCO < 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol.
Patient or guardian able to sign informed consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Damiano Rondelli, MD | University of Illinois at Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois at Chicago Medical Center | Chicago | Illinois | 60612 | United States |
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Criteria for FluBu conditioning: <60 years old; no diagnosis of myeloma or myelofibrosis (MF) in chronic phase; and not having received an autologous stem cell transplant with the last 2 years. Patients not fulfilling these criteria but still eligible for allogeneic transplantation were prepared with FluMel.
We analyzed the clinical outcome of patients with hematological malignancies at standard or high-risk, who were transplanted (allogeneic peripheral blood or BMT HSCT) after receiving FluBU as a conditioning regimen. A total of 30 patients were recruited for this study which was conducted at the UIC Medical Center Inpatient BMT unit.
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| ID | Title | Description |
|---|---|---|
| FG000 | Fludarabine/Busulfan + ATG | All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor. fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| fludarabine/ melphalan | Drug | All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl). |
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| ATG | Drug | Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen. |
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Days to ANC or platelet engraftment
| Up to 30 days post-transplant |
| Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD). | Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant. | Up to 100 days post-transplant (acute GVHD). |
| FG001 | Fludarabine/Melphalan + ATG | All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG. fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl). |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 | All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor. fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI. |
| BG001 | Arm 2 | All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG. fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Engraftment. | Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant. | Posted | Number | participants | Up to 30 days post-transplant |
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| ||||||||||||||||||||||||||||||
| Secondary | Participants With 100 Day Transplant-related Mortality. | Day 100 transplant-related mortality was measured in both groups. | Posted | Number | participants | Up to 100 days post-transplant. |
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| |||||||||||||||||||||||||||||||
| Secondary | Time to ANC and Platelet Engraftment | Days to ANC or platelet engraftment | Posted | Median | Full Range | days to ANC and platelet engraftment | Up to 30 days post-transplant |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD). | Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant. | Posted | Number | participants | Up to 100 days post-transplant (acute GVHD). |
|
365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Extra-hematological Toxicities | We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and FluMel and receiving PBSC. | 8 | 30 | 0 | 30 | ||
| EG001 | FluBu Participants With Extra-hematological Toxicities | We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and receiving PBSC. | 5 | 18 | 0 | 18 | ||
| EG002 | FluMel Participants With Extra-hematological Toxicities | We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluMel and receiving PBSC. | 3 | 12 | 0 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| stomatitis | Gastrointestinal disorders | Bearman criteria | Systematic Assessment |
| |
| CMV reactivation | Immune system disorders | Bearman criteria | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Veno-occlusive disease | Hepatobiliary disorders | Bearman criteria | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Damiano Rondelli, MD | University of Illinois Cancer Center | 312-996-6179 | drond@uic.edu |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D008223 | Lymphoma |
| D006689 | Hodgkin Disease |
| D009101 | Multiple Myeloma |
| D007945 | Leukemia, Lymphoid |
| D009196 | Myeloproliferative Disorders |
| D011087 | Polycythemia Vera |
| D055728 | Primary Myelofibrosis |
| D000741 | Anemia, Aplastic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D012008 | Recurrence |
| D001752 | Blast Crisis |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D019046 | Bone Marrow Neoplasms |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
| D000740 | Anemia |
| D000080983 | Bone Marrow Failure Disorders |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D015448 | Leukemia, B-Cell |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| D002066 | Busulfan |
| C042382 | fludarabine phosphate |
| D008558 | Melphalan |
| C512542 | thymoglobulin |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Participants |
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