Prevention and Reduction Of GvHD and Relapse and Enhancing Survival after Stem cell transplantatio
- Conditions
- Acute Leukemia in morphologic complete remissionMyelodisplasia with less than 5% blasts in the marrow and no circulating blastsMedDRA version: 20.1Level: LLTClassification code 10024330Term: Leukemia acuteSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2015-000602-18-DE
- Lead Sponsor
- ational Heart, Lung, and Blood Institute (NHLBI)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 345
1. Males and females aged = 1.0 year and < 66.0 years
2. Patients with acute leukemia in morphologic complete remission with or without hematologic recovery or with myelodysplasia (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow. Patients with CMML must have a WBC count =10,000 cells/µL and <5% blasts in the marrow. Patients with = 5% blasts due to a regenerating marrow must contact the protocol chairs for review.
3. Planned myeloablative conditioning regimen (see eligible regimens in Table 2.4)
4. Patients must have a related or unrelated donor as follows:
a. Related donor must be an 8/8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing. Pediatric related donors must weigh = 25.0 kg., must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter, must be willing to (1) donate bone marrow and (2) receive G-CSF followed by donation of peripheral blood stem cells (product to be determined by randomization post enrollment) and must meet institutional criteria for donation1.
b. Unrelated donor must be an 8/8 match at HLA-A, -B, -C and –DRB1 at high resolution using DNA-based typing. Unrelated donor must be medically eligible to donate according to NMDP (or equivalent donor search organization) criteria. At time of enrollment, the donor should not have any known preferences or contraindications to donate bone marrow or peripheral blood stem cells .
i. Selection of unrelated donors is to be performed according to institutional practice. It is recommended that the time from collection to initiation of the cell processing be considered when prioritizing donors, as data shows better results for CD34 selection when cell processing begins within 36 hours of the end of collection as indicated in section 2.5.1.2.
5. Cardiac function: Ejection fraction at rest =45.0% or shortening fraction of = 27.0% by echocardiogram or radionuclide scan (MUGA).
6. Estimated creatinine clearance (for patients > 12 years) greater than 50.0 mL/minute (using the Cockcroft-Gault formula and actual body weight); for pediatric patients (= 1 year to 12 years), GFR estimated by the updated Schwartz formula = 90.0 mL/min/1.73 m2. If the estimated creatinine clearance is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 70.0 mL/min/1.73 m2.
7. Pulmonary function: DLCO =50% (adjusted for hemoglobin), and FVC and FEV1=50%; for children who are unable to perform for PFTs due to age or developmental ability, there must be no evidence of dyspnea and no need for supplemental oxygen, as evidenced by O2 saturation = 92% on room air.
8. Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert’s Syndrome) and ALT/AST < 2.5x the upper limit of normal.
9. Signed informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 345
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Prior autologous or allogeneic hematopoietic stem cell transplant
2. Karnofsky or Lansky Performance Score < 70%
3. Active CNS involvement by malignant cells
4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
5. Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
6. Patients seropositive for HIV-1 or -2
7. Patients seropositive for HTLV-I or -II
8. Patients with active Hepatitis B or C viral replication by PCR
9. Documented allergy to iron dextran or murine proteins
10. Women who are pregnant (positive serum or urine ßHCG) or breastfeeding
11. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use 2 effective forms of birth control or abstinence for one year after transplantation
12. History of uncontrolled autoimmune disease or on active treatment
13. Patients with prior malignancies, except resected non-melanoma or treated cervical carcinoma in situ. Cancer treated with curative intent = 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
14. Patient unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests
15. Planned post-transplant maintenance therapy except for FLT3 inhibitors or TKIs
a. Must be declared prior to randomization.
16. If it is known prior to enrollement that the hematopoietic stem cell product will need to be cryopreserved, the patient should not be enrolled.
17. German centers only: Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or participation in any other interventional clinical study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the randomized trial is to compare chronic GVHD/relapse-free survival (CRFS) after HSCT across two CNI-free interventions and Tac/Mtx control. <br>;Secondary Objective: Comparison:<br>Overall survival<br>Grades II-IV and III-IV acute GVHD<br>Chronic GVHD <br>Immunosuppression-free survival at 1 year<br>Hematologic recovery<br>Primary and secondary graft failure<br>Disease relapse or progression<br>Transplant-related mortality<br>Toxicity and rates of infections (CMV and EBV reactivation)<br>Disease-free survival<br>Immune reconstitution<br>Quality of Life<br>;Primary end point(s): Chronic GVHD/relapse-free survival (CRFS): this time to event outcome is defined as moderate to severe chronic GVHD by the NIH consensus criteria, disease relapse, or death by any cause. ;Timepoint(s) of evaluation of this end point: Baseline assumption of 22% by 1 year
- Secondary Outcome Measures
Name Time Method