Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies (IM-TMI)
Primary Purpose
Acute Myeloid Leukemia, Lymphoblastic Leukemia, Acute Leukemia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
IM-TMI (3Gy)
IM-TMI (6Gy)
IM-TMI (9Gy)
IM-TMI (12Gy)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring total marrow irradiation, intensity modulated radiation, leukemia, hematologic diseases
Eligibility Criteria
Inclusion Criteria:
Patients with the following diseases:
- Acute myeloid or lymphoblastic leukemia in first complete remission if poor prognosis documented by failure to response after initial induction chemotherapy, or cytogenetic, or molecular studies.
- Acute leukemia in greater/equal second remission, or partial remission after chemotherapy.
- High grade non Hodgkin's or Hodgkin's lymphoma with marrow involvement resistant/ relapsed after second line therapy including high dose chemotherapy and autologous SCT.
- CML in advanced or blastic phase.
- Plasma cell leukemia.
- 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:
- Life expectancy is severely limited by concomitant illness.
- Evidence of chronic active hepatitis or cirrhosis
- HIV-positive
- Patient is pregnant
- Patient or guardian is not able to sign informed consent.
Sites / Locations
- University of Illinois at Chicago
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
IM-TMI (3Gy)
IM-TMI (6Gy)
IM-TMI (9Gy)
IM-TMI (12Gy)
Arm Description
Patients will receive 3Gy per day for 1 day (total of 3Gy).
Patients will receive 3Gy per day for 2 days (for a total of 6Gy).
Patients will receive 3Gy per day for 3 days (for a total of 9Gy).
Patients will receive 3Gy per day for 4 days (for a total of 12Gy).
Outcomes
Primary Outcome Measures
Number of Participants With Grade 4 TMI Toxicity
Number of Participants With 1 Year Mortality Unrelated to TMI
Secondary Outcome Measures
Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies
Full Information
NCT ID
NCT00988013
First Posted
September 30, 2009
Last Updated
May 18, 2021
Sponsor
University of Illinois at Chicago
1. Study Identification
Unique Protocol Identification Number
NCT00988013
Brief Title
Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies
Acronym
IM-TMI
Official Title
A Phase I Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Illinois at Chicago
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Lymphoblastic Leukemia, Acute Leukemia, Non Hodgkins Lymphoma, Chronic Myeloid Leukemia
Keywords
total marrow irradiation, intensity modulated radiation, leukemia, hematologic diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Dose escalation of total marrow irradiation prior to stem cell transplantation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IM-TMI (3Gy)
Arm Type
Experimental
Arm Description
Patients will receive 3Gy per day for 1 day (total of 3Gy).
Arm Title
IM-TMI (6Gy)
Arm Type
Experimental
Arm Description
Patients will receive 3Gy per day for 2 days (for a total of 6Gy).
Arm Title
IM-TMI (9Gy)
Arm Type
Experimental
Arm Description
Patients will receive 3Gy per day for 3 days (for a total of 9Gy).
Arm Title
IM-TMI (12Gy)
Arm Type
Experimental
Arm Description
Patients will receive 3Gy per day for 4 days (for a total of 12Gy).
Intervention Type
Radiation
Intervention Name(s)
IM-TMI (3Gy)
Intervention Description
Patients will receive 3Gy per day for 1 day.
Intervention Type
Radiation
Intervention Name(s)
IM-TMI (6Gy)
Intervention Description
Patients will receive 3Gy per day for 2 days.
Intervention Type
Radiation
Intervention Name(s)
IM-TMI (9Gy)
Intervention Description
Patients will receive 3Gy per day for 3 days.
Intervention Type
Radiation
Intervention Name(s)
IM-TMI (12Gy)
Intervention Description
Patients will receive 3Gy per day for 4 days.
Primary Outcome Measure Information:
Title
Number of Participants With Grade 4 TMI Toxicity
Time Frame
1 year post-transplant
Title
Number of Participants With 1 Year Mortality Unrelated to TMI
Time Frame
1 year post-transplant
Secondary Outcome Measure Information:
Title
Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies
Time Frame
Up to 100 days post-transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with the following diseases:
Acute myeloid or lymphoblastic leukemia in first complete remission if poor prognosis documented by failure to response after initial induction chemotherapy, or cytogenetic, or molecular studies.
Acute leukemia in greater/equal second remission, or partial remission after chemotherapy.
High grade non Hodgkin's or Hodgkin's lymphoma with marrow involvement resistant/ relapsed after second line therapy including high dose chemotherapy and autologous SCT.
CML in advanced or blastic phase.
Plasma cell leukemia.
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:
Life expectancy is severely limited by concomitant illness.
Evidence of chronic active hepatitis or cirrhosis
HIV-positive
Patient is pregnant
Patient or guardian is not able to sign informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damiano Rondelli, MD
Organizational Affiliation
University of Illinois at Chicago
Official's Role
Study Chair
Facility Information:
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35851593
Citation
Tran MC, Hasan Y, Wang A, Yenice K, Partouche J, Stock W, Larson RA, Kosuri S, LaBelle JL, Kline J, Riedell PA, Artz AS, Weichselbaum R, Bishop MR, Aydogan B, Liu H. A phase 1 trial utilizing TMI with fludarabine-melphalan in patients with hematologic malignancies undergoing second allo-SCT. Blood Adv. 2023 Feb 14;7(3):285-292. doi: 10.1182/bloodadvances.2022007530.
Results Reference
derived
PubMed Identifier
25234438
Citation
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.
Results Reference
derived
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Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies
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