Myeloid Hematological Malignancies Clinical Trial
— UCAMLOfficial title:
Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)
| NCT number | NCT01247701 |
| Other study ID # | 26558-UCAML |
| Secondary ID | |
| Status | Completed |
| Phase | N/A |
| First received | |
| Last updated | |
| Start date | November 2010 |
| Est. completion date | October 2019 |
| Verified date | May 2022 |
| Source | Baylor College of Medicine |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
In this study, the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell Transplant (SCT) regimen. As an attempt to improve engraftment rate and reduce infections, the investigators are going to incorporate fludarabine in the conditioning regimen. The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide (Cy/TBI) regimen. Encouraging data on adding fludarabine to the SCT regimen have been reported. A fludarabine-based, conditioning regimen, with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality. Regimen-related toxicity is believed to be a major contributing factor to GVHD. Therefore this approach may also lead to reduced GVHD, as some investigators have suggested. In an attempt to decrease the rate of viral infection and reactivation, the investigators will avoid ATG (Thymoglobulin) / Campath (anti-CD52), and instead administer Mycophenolate Mofetil (MMF). The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATG/Campath. The investigators anticipate that the removal of ATG/Campath will facilitate immune reconstitution more efficiently after receiving a UCBT.
| Status | Completed |
| Enrollment | 16 |
| Est. completion date | October 2019 |
| Est. primary completion date | October 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 17 Years |
| Eligibility | Inclusion Criteria: - Patients with a myeloid hematologic malignancy (acute myelogenous leukemia, secondary myelogenous leukemia or myelodysplastic syndrome) unlikely to be cure by standard chemotherapy. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostics features. - Related or Unrelated Umbilical Cord Blood Unit with 0-1 antigen mismatch at HLA-A and B (at low resolution) and DRB1 (at high resolution), with a total nucleated cell dose of = 4 x 10^7/kg. - Lansky/Karnofsky scores at least 60. - Written informed consent and/or signed assent line from patient, parent or guardian. - Negative pregnancy test, if applicable. Exclusion Criteria: - Patients with uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. - Severe renal disease (Creatinine > 3X normal for age). - Severe hepatic disease (direct bilirubin > 3 mg/dL or SGOT > 500). - Patient has DLCO < 50% predicted or FEV1 < 50% of predicted, if applicable. - Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction < 20%). - HIV positive. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Texas Children's Hospital | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients. | To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies. | 100 days, 1 year, and 3 years | |
| Secondary | Number of Participants With Severe Acute GVHD Grade III-IV | Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD. | Day 100 | |
| Secondary | Number of Participants With Chronic GvHD | Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3. | 1 year | |
| Secondary | Number of Participants With Relapse Rate After Transplant | To assess relapse rate at 1 and 3 years after transplant. Cumulative incidence of relapse was calculated from the date of umbilical cord blood transplant using the competing risk method as described in Gray(1988) with death prior to relapse as the competing risk. Participants still alive without a date of relapse were censored at the time of the last follow-up. | 1 and 3 years | |
| Secondary | Number of Participants With Donor Engraftment After Transplant. | To evaluate donor engraftment at 100 days, 6, 9, 12, 24, and 36 months after transplant. | 100 days, 6, 9, 12, 24 and 36 months | |
| Secondary | Number of Participants With Platelet Engraftment | Achievement of untransfused platelet count > 20 x 10^9/L on three consecutive days | Day 180 | |
| Secondary | Number of Participants With Neutrophil Engraftment | Achievement of absolute neutrophil count > 0.5 x 10^9/L on three consecutive days | Day 42 |