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

NCT00988013 | Completed Results DMC

• 1 other identifier: 2009-0251
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Keywords

total marrow irradiation; intensity modulated radiation; leukemia; hematologic diseases

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (1)

• Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies

  Up to 100 days post-transplant

Study Arms (4)

IM-TMI (3Gy)

EXPERIMENTAL

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

Radiation: IM-TMI (3Gy)

IM-TMI (6Gy)

EXPERIMENTAL

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

Radiation: IM-TMI (6Gy)

IM-TMI (9Gy)

EXPERIMENTAL

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

Radiation: IM-TMI (9Gy)

IM-TMI (12Gy)

EXPERIMENTAL

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

Radiation: IM-TMI (12Gy)

Interventions

IM-TMI (3Gy) RADIATION

Patients will receive 3Gy per day for 1 day.

IM-TMI (3Gy)

IM-TMI (6Gy) RADIATION

Patients will receive 3Gy per day for 2 days.

IM-TMI (6Gy)

IM-TMI (9Gy) RADIATION

Patients will receive 3Gy per day for 3 days.

IM-TMI (9Gy)

IM-TMI (12Gy) RADIATION

Patients will receive 3Gy per day for 4 days.

IM-TMI (12Gy)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• 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.

  PMID: 25234438 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Hematologic Diseases

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Damiano Rondelli
• Organization: University of Illinois at Chicago

drond@uic.edu

312-996-6179

Study Officials

• Damiano Rondelli, MD

  University of Illinois at Chicago

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Dose escalation of total marrow irradiation prior to stem cell transplantation

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: June 14, 2021
• Results First Posted: June 14, 2021

Record last verified: 2021-05

Locations

US (1)