Clinical trial NCT00988013: Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies
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
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myeloid Leukemia
Lymphoblastic Leukemia
Acute Leukemia
Non Hodgkins Lymphoma
Chronic Myeloid Leukemia
Keywords: total marrow irradiation
intensity modulated radiation
leukemia
hematologic diseases
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2009-10-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Dose escalation of total marrow irradiation prior to stem cell transplantation
Primary purpose: TREATMENT

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%.


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.

Primary outcomes:
measure: Number of Participants With Grade 4 TMI Toxicity
timeFrame: 1 year post-transplant
measure: Number of Participants With 1 Year Mortality Unrelated to TMI
timeFrame: 1 year post-transplant
Secondary outcomes:
measure: Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies
timeFrame: Up to 100 days post-transplant
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Damiano Rondelli, MD
role: STUDY_CHAIR
References:
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.
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.