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This is a phase I study using Intensity Modulated Total Marrow Irradiation (IM-TMI) in addition to a chemotherapy regimen in preparation for an allogeneic stem cell transplant for advanced hematologic malignancies such as acute myeloid or lymphoblastic leukemia, high grade non Hodgkin's or Hodgkin's lymphoma, chronic myelogenous leukemia, and plasma cell leukemia. Because the subjects participating in this study have a disease that is severe and has a high risk of relapse even after transplant, the investigators propose to use a chemotherapy regimen (fludarabine/busulfan), the name for the combination of chemotherapy drugs that is given to patients prior to transplantation of the donor stem cells, along with intensity modulated radiation (IM-TMI) to the bone marrow. Total body irradiation (TBI) in conjunction with chemotherapy is a standard of care as a pre-conditioning regimen prior to bone marrow transplant (BMT) in patients with hematologic malignancies. However, TBI can cause severe side effects due to irradiation of organs such as the lenses of the eye, whole brain, lungs, liver, kidneys, heart, small bowel and oral cavity. IM-TMI allows for the delivery of adequate doses of radiation to the bone marrow while sparing other organs and therefore limiting radiation side effects. The irradiation, along with receiving the chemotherapy drugs will suppress the subject's immune system and kill off tumor cells, but will also intensify the effect of the conditioning regimen thus allowing the bone marrow transplantation to have a greater chance of being successful.
No investigational drugs are used in this study. The investigational part of this study is the use of intensity modulated total marrow irradiation instead of conventional radiation. IMTMI can deliver 99% of the prescribed treatment to the targeted bones and reduce the doses of radiation to surrounding organs, as received in conventional TBI, by 29% to 65%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IM-TMI (3Gy) | Experimental | Patients will receive 3Gy per day for 1 day (total of 3Gy). |
|
| IM-TMI (6Gy) | Experimental | Patients will receive 3Gy per day for 2 days (for a total of 6Gy). |
|
| IM-TMI (9Gy) | Experimental | Patients will receive 3Gy per day for 3 days (for a total of 9Gy). |
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| IM-TMI (12Gy) | Experimental | Patients will receive 3Gy per day for 4 days (for a total of 12Gy). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IM-TMI (3Gy) | Radiation | Patients will receive 3Gy per day for 1 day. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Grade 4 TMI Toxicity | 1 year post-transplant | |
| Number of Participants With 1 Year Mortality Unrelated to TMI | 1 year post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | Up to 100 days post-transplant |
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Inclusion Criteria:
Patients with the following diseases:
Age 18-60 years.
Karnofsky performance status of 70
Adequate cardiac and pulmonary function. Patients with decreased LVEF less than/equal to 40% or DLCO less than/equal to 50% of predicted will require clearance from cardiology or pulmonary services, respectively, prior to enrollment on this protocol.
Serum creatinine less than/equal to 1.5 mg/dL or Creatinine Clearance greater than/equal to 50 ml/min .
Serum bilirubin 2.0 mg/dl, SGPT less than/equal to 3 times the upper limit of normal
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Damiano Rondelli, MD | University of Illinois at Chicago | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois at Chicago | Chicago | Illinois | 60612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25234438 | Derived | Patel P, Aydogan B, Koshy M, Mahmud D, Oh A, Saraf SL, Quigley JG, Khan I, Sweiss K, Mahmud N, Peace DJ, DeMasi V, Awan AM, Weichselbaum RR, Rondelli D. Combination of linear accelerator-based intensity-modulated total marrow irradiation and myeloablative fludarabine/busulfan: a phase I study. Biol Blood Marrow Transplant. 2014 Dec;20(12):2034-41. doi: 10.1016/j.bbmt.2014.09.005. Epub 2014 Sep 16. |
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| ID | Title | Description |
|---|---|---|
| FG000 | IM-TMI (3Gy) | Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day. |
| FG001 | IM-TMI (6Gy) | Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Dose escalation of total marrow irradiation prior to stem cell transplantation
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| IM-TMI (6Gy) |
| Radiation |
Patients will receive 3Gy per day for 2 days. |
|
| IM-TMI (9Gy) | Radiation | Patients will receive 3Gy per day for 3 days. |
|
| IM-TMI (12Gy) | Radiation | Patients will receive 3Gy per day for 4 days. |
|
| FG002 | IM-TMI (9Gy) | Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days. |
| FG003 | IM-TMI (12Gy) | Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days. |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | IM-TMI (3Gy) | Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day. |
| BG001 | IM-TMI (6Gy) | Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days. |
| BG002 | IM-TMI (9Gy) | Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days. |
| BG003 | IM-TMI (12Gy) | Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days. |
| BG004 | 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, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Median | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | 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 Grade 4 TMI Toxicity | Posted | Count of Participants | Participants | 1 year post-transplant |
|
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | Posted | Median | Full Range | Days | Up to 100 days post-transplant |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With 1 Year Mortality Unrelated to TMI | Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 | Posted | Count of Participants | Participants | 1 year post-transplant |
|
7 years
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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 | IM-TMI (3Gy) | Patients will receive 3Gy per day for 1 day (total of 3Gy). IM-TMI (3Gy): Patients will receive 3Gy per day for 1 day. | 1 | 3 | 0 | 3 | 3 | 3 |
| EG001 | IM-TMI (6Gy) | Patients will receive 3Gy per day for 2 days (for a total of 6Gy). IM-TMI (6Gy): Patients will receive 3Gy per day for 2 days. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG002 | IM-TMI (9Gy) | Patients will receive 3Gy per day for 3 days (for a total of 9Gy). IM-TMI (9Gy): Patients will receive 3Gy per day for 3 days. | 4 | 6 | 2 | 6 | 6 | 6 |
| EG003 | IM-TMI (12Gy) | Patients will receive 3Gy per day for 4 days (for a total of 12Gy). IM-TMI (12Gy): Patients will receive 3Gy per day for 4 days. | 2 | 2 | 2 | 2 | 2 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| GVHD | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Liver failure | Hepatobiliary disorders | Systematic Assessment |
| ||
| Bronchiolitis | Infections and infestations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oral mucositis | Infections and infestations | Systematic Assessment |
| ||
| Gut mucocitis | Gastrointestinal disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Damiano Rondelli | University of Illinois at Chicago | 312-996-6179 | drond@uic.edu |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D008228 | Lymphoma, Non-Hodgkin |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008223 | Lymphoma |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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