A phase II trial of sequential treatment with cytoreductive therapy and reduced intensity conditioning allogeneic stem cell transplantation for relapsed/ refractory acute myeloid leukemia, high risk myelodysplasia, or other high risk myeloid malignancies

• Register: ISRCTN
• Last refreshed on: 19 April 2022
• Main ID: ISRCTN32336114
• Date of registration: 27/03/2007
• Prospective Registration: Yes
• Primary sponsor: Barts and the London NHS Trust (UK)
• Public title: A phase II trial of sequential treatment with cytoreductive therapy and reduced intensity conditioning allogeneic stem cell transplantation for relapsed/ refractory acute myeloid leukemia, high risk myelodysplasia, or other high risk myeloid malignancies
• Scientific title: A phase II trial of sequential treatment with cytoreductive therapy and reduced intensity conditioning allogeneic stem cell transplantation for relapsed/ refractory acute myeloid leukemia, high risk myelodysplasia, or other high risk myeloid malignancies
• Date of first enrolment: 01/04/2007
• Target sample size: 93
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN32336114
• Study type: Interventional
• Study design: Open phase II study (Treatment)
• Phase: Phase II

Countries of recruitment

England, United Kingdom

Contacts

• Name: Jamie Cavenagh

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of histologically documented acute myeloid leukemia (AML) (any WHO type), with primary induction failure, or at relapse where the patient is not a candidate or does not wish to proceed to a myeloablative transplant. Also, histologically / cytogenetically documented diagnosis of Myelodysplasia (MDS) (IPSS Int. 2, HR) , or other high risk Myeloid Malignancy where the patient is not a candidate or does not wish to proceed to a myeloablative transplant.
2. All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) (Version 3.0) Grade < 2 (with the exception of chemotherapy-induced alopecia). Surgery must have occurred at least 21 days prior to initiation of treatment.
3. Age must be greater than 18 years.
4. Last dose of antineoplastic therapy must be more than 14 days from starting treatment, except for hydroxyurea or Low Dose Ara C which may have been administered up to 24 hours prior to first study drug administration for leukoreduction.
5. Eastern Cooperative Oncology Group (ECOG) performance status must be 0, 1, or 2.
6. Life expectancy of at least 2 months.
7. Pregnancy test (females of childbearing potential) Negative.
8. Signed informed consent indicating that they are aware of the neoplastic nature of their disease and have been informed of the procedures to be followed, alternatives, potential benefits, side effects, risks, and discomforts.
9. Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.

Exclusion criteria:
1. Concurrent therapy with any other investigational agent.
2. Pregnant or breastfeeding women. All at-risk female subjects must have a negative pregnancy test within 10 days prior to the start treatment.
3. Clinically significant cardiac disease (New York Heart Association, Class III or IV).
4. Dementia or altered mental status that would prohibit informed consent.
5. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study.
6. Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Myeloid malignancies
Cancer
Myeloid malignancies

Intervention(s)

Reduced intensity conditioning allogeneic stem cell transplantation: standard practice calls for remission (or near remission) in patients treated with chemotherapy before progression to transplantation. This occurs in less than 50% of cases. In this study, all patients will proceed straight to transplantation.

Primary Outcome(s)

Overall Survival (OS) at 1, 2 and 4 years

Secondary Outcome(s)

1. Event Free Survival (EFS) at 1, 2 and 4 years
2. Treatment Related Mortality (TRM) at d100, 1 and 2 years and cause of mortality
3. Incidence and Grade of Acute Graft versus Host Disease (GVHD)
4. Incidence and Grade of Chronic GVHD
5. Time to Engraftment*
6. Full Split Chimerism at Days 30, 60, 100 and 1 year
7. Request for Donor Lymphocyte Infusion (DLI) (Mixed chimerism vs disease persistence)
8. Incidence of opportunistic infections
9. Duration of hospitalisation
*Date of Neutrophil Engraftment is defined as the first of two consecutive days with a neutrophil count exceeding 500/µL. Date of platelet recovery is considered the first of three consecutive days with an unsupported platelet count exceeding 20 x 109 / L.

Secondary ID(s)

2007-000806-64

BLT004973

Source(s) of Monetary Support

Barts and the London NHS Trust (UK)

Ethics review

Status:
Approval date:
Contact:

East London and The City Committee 1, 23/07/2007, ref: 07/Q0603/65

Results

• Results available: Yes
• Date Completed: 01/04/2011