Intensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies

NCT ID: NCT00988013

Last Updated: 2021-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2016-02-29

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%.

Conditions

Acute Myeloid Leukemia; Lymphoblastic Leukemia; Acute Leukemia; Non Hodgkins Lymphoma; Chronic Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IM-TMI (3Gy)

Patients will receive 3Gy per day for 1 day (total of 3Gy).

Group Type: EXPERIMENTAL

IM-TMI (3Gy)

Intervention Type: RADIATION

Patients will receive 3Gy per day for 1 day.

IM-TMI (6Gy)

Patients will receive 3Gy per day for 2 days (for a total of 6Gy).

Group Type: EXPERIMENTAL

IM-TMI (6Gy)

Intervention Type: RADIATION

Patients will receive 3Gy per day for 2 days.

IM-TMI (9Gy)

Patients will receive 3Gy per day for 3 days (for a total of 9Gy).

Group Type: EXPERIMENTAL

IM-TMI (9Gy)

Intervention Type: RADIATION

Patients will receive 3Gy per day for 3 days.

IM-TMI (12Gy)

Patients will receive 3Gy per day for 4 days (for a total of 12Gy).

Group Type: EXPERIMENTAL

IM-TMI (12Gy)

Intervention Type: RADIATION

Patients will receive 3Gy per day for 4 days.

Interventions

IM-TMI (3Gy)

Patients will receive 3Gy per day for 1 day.

Intervention Type: RADIATION

IM-TMI (6Gy)

Patients will receive 3Gy per day for 2 days.

Intervention Type: RADIATION

IM-TMI (9Gy)

Patients will receive 3Gy per day for 3 days.

Intervention Type: RADIATION

IM-TMI (12Gy)

Patients will receive 3Gy per day for 4 days.

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Damiano Rondelli, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Damiano Rondelli, MD

Role: STUDY_CHAIR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25234438 (View on PubMed)

Other Identifiers

2009-0251

Identifier Type: -

Identifier Source: org_study_id