Trial Outcomes & Findings for Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients (NCT NCT00499889)

NCT ID: NCT00499889

Last Updated: 2012-04-23

Results Overview

Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Baseline to 1 year

Results posted on

2012-04-23

Participant Flow

Recruitment Period: 02/12/03 to 01/15/09. All patients were recruited at UT MD Anderson Cancer Center.

One patient registered for transplant became ineligible before any treatment due to infection and was taken off study; 41 patients received the transplant regimen and an Allogeneic transplant.

Participant milestones

Participant milestones
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Overall Study
STARTED
42
Overall Study
COMPLETED
41
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Overall Study
Infection prior to treatment
1

Baseline Characteristics

Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=42 Participants
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Age, Categorical
<=18 years
1 Participants
n=99 Participants
Age, Categorical
Between 18 and 65 years
39 Participants
n=99 Participants
Age, Categorical
>=65 years
2 Participants
n=99 Participants
Age Continuous
42.2 years
FULL_RANGE 42 • n=99 Participants
Sex: Female, Male
Female
20 Participants
n=99 Participants
Sex: Female, Male
Male
22 Participants
n=99 Participants
Region of Enrollment
United States
42 participants
n=99 Participants

PRIMARY outcome

Timeframe: Baseline to 1 year

Population: Analysis was per protocol. One patient did not receive treatment and was excluded from analysis.

Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).

Outcome measures

Outcome measures
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=41 Participants
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Number of Participants in Complete Molecular Remission at 1 Year
21 participants

SECONDARY outcome

Timeframe: 1 Year

Population: Analysis was per protocol. Only 19 participants having the post transplant Imatinib Mesylate Therapy out of the 41 participants treated were analyzed for this outcome.

Number of participants with response of molecular complete remission (mCR) to Imatinib Mesylate therapy as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.

Outcome measures

Outcome measures
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=19 Participants
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy
10 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Only 8 participants having the post-transplant DLI out of the 41 participants treated were analyzed for this outcome.

Number of participants with response of molecular complete remission (mCR) to DLI as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.

Outcome measures

Outcome measures
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=8 Participants
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Participants' With mCR Response to Post Transplant DLI
4 Participants

Adverse Events

Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin

Serious events: 12 serious events
Other events: 37 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=41 participants at risk
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Blood and lymphatic system disorders
severe anemia
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Hepatobiliary disorders
increased bilirubin
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Infections and infestations
Neutropenic Fever
4.9%
2/41 • Number of events 2 • 5 years and 6 months
Nervous system disorders
neurologic
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Skin and subcutaneous tissue disorders
Urticaria
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Gastrointestinal disorders
Abdominal Distention
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Cardiac disorders
Hypertensive Crisis
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Blood and lymphatic system disorders
Thrombocytopenia
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Blood and lymphatic system disorders
Myelosupression
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Immune system disorders
GVHD
4.9%
2/41 • Number of events 2 • 5 years and 6 months

Other adverse events

Other adverse events
Measure
Mesylate, Busulfan, Fludarabine + Antithymocyte Globulin
n=41 participants at risk
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Hepatobiliary disorders
increased LDH
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Infections and infestations
infection
14.6%
6/41 • Number of events 6 • 5 years and 6 months
Infections and infestations
decreased neutrpoenia
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Nervous system disorders
neurolgic other
4.9%
2/41 • Number of events 2 • 5 years and 6 months
Nervous system disorders
headache
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Nervous system disorders
drowiness
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Respiratory, thoracic and mediastinal disorders
shortness of breath
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Respiratory, thoracic and mediastinal disorders
pneumonia
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Skin and subcutaneous tissue disorders
skin other
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Skin and subcutaneous tissue disorders
skin rash
12.2%
5/41 • Number of events 5 • 5 years and 6 months
Blood and lymphatic system disorders
Granulocytes
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Blood and lymphatic system disorders
platelets
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Cardiac disorders
increased blood pressure
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Blood and lymphatic system disorders
increased prothrombin time
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Infections and infestations
fever
9.8%
4/41 • Number of events 4 • 5 years and 6 months
General disorders
fatigue
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Gastrointestinal disorders
Gastrointestional Disorder (other)
4.9%
2/41 • Number of events 2 • 5 years and 6 months
Gastrointestinal disorders
esophagitis
9.8%
4/41 • Number of events 4 • 5 years and 6 months
Gastrointestinal disorders
nausea
9.8%
4/41 • Number of events 4 • 5 years and 6 months
Gastrointestinal disorders
diarrhea
2.4%
1/41 • Number of events 1 • 5 years and 6 months
Hepatobiliary disorders
increased alanine aminotransferase (ALT)
2.4%
1/41 • Number of events 1 • 5 years and 6 months

Additional Information

Richard E. Champlin, MD/Professor

UT MD Anderson Cancer Center

Phone: 713-792-8848

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place