Acute Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Lymphoblastic Leukemia, Non Hodgkins Lymphoma
Conditions
Keywords
total marrow irradiation, intensity modulated radiation, leukemia, hematologic diseases
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%.
Interventions
RADIATIONIM-TMI (3Gy)
Patients will receive 3Gy per day for 1 day.
RADIATIONIM-TMI (6Gy)
Patients will receive 3Gy per day for 2 days.
RADIATIONIM-TMI (9Gy)
Patients will receive 3Gy per day for 3 days.
RADIATIONIM-TMI (12Gy)
Patients will receive 3Gy per day for 4 days.
Sponsors
University of Illinois at Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation of total marrow irradiation prior to stem cell transplantation
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame |
|---|---|
| Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | Up to 100 days post-transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 3 |
| 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. | 6 |
| 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 |
| Total | 14 |
Baseline characteristics
| Characteristic | IM-TMI (3Gy) | IM-TMI (6Gy) | IM-TMI (9Gy) | IM-TMI (12Gy) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 14 Participants |
| Age, Continuous | 52 Years | 38 Years | 39 Years | 53 Years | 52 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 11 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 3 | 4 / 6 | 2 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 2 / 6 | 2 / 2 |
Outcome results
Primary
Number of Participants With 1 Year Mortality Unrelated to TMI
Time frame: 1 year post-transplant
Population: Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0 Grade 4 TMI toxicity 0
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM-TMI (3Gy) | Number of Participants With 1 Year Mortality Unrelated to TMI | 0 Participants |
| IM-TMI (6Gy) | Number of Participants With 1 Year Mortality Unrelated to TMI | 0 Participants |
| IM-TMI (12Gy) | Number of Participants With 1 Year Mortality Unrelated to TMI | 2 Participants |
| IM-TMI (9Gy) | Number of Participants With 1 Year Mortality Unrelated to TMI | 2 Participants |
Primary
Number of Participants With Grade 4 TMI Toxicity
Time frame: 1 year post-transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM-TMI (3Gy) | Number of Participants With Grade 4 TMI Toxicity | 0 Participants |
| IM-TMI (6Gy) | Number of Participants With Grade 4 TMI Toxicity | 0 Participants |
| IM-TMI (12Gy) | Number of Participants With Grade 4 TMI Toxicity | 0 Participants |
| IM-TMI (9Gy) | Number of Participants With Grade 4 TMI Toxicity | 2 Participants |
Secondary
Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies
Time frame: Up to 100 days post-transplant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IM-TMI (3Gy) | Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | 15 Days |
| IM-TMI (6Gy) | Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | 15 Days |
| IM-TMI (12Gy) | Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | 15 Days |
| IM-TMI (9Gy) | Time to Neutrophil and Platelet Engraftment in Patients With Hematologic Malignancies | 15 Days |