ARM C: nonrandomized haploHCT for Stem Cell Transplantation

Phase-Based Progress Estimates
2
Effectiveness
3
Safety
Stem Cell Transplantation+5 Morematched unrelated donor hematopoietic cell transplantation (MUD-HCT) - Procedure
Eligibility
6 - 22
All Sexes
What conditions do you have?
Select

Study Summary

This phase III trial compares hematopoietic (stem) cell transplantation (HCT) using mismatched related donors (haploidentical [haplo]) versus matched unrelated donors (MUD) in treating children, adolescents, and young adults with acute leukemia or myelodysplastic syndrome (MDS). HCT is considered standard of care treatment for patients with high-risk acute leukemia and MDS. In HCT, patients are given very high doses of chemotherapy or radiation therapy, which is intended to kill cancer cells that may be resistant to more standard doses of chemotherapy; unfortunately, this also destroys the normal cells in the bone marrow, including stem cells. After the treatment, patients must have a healthy supply of stem cells reintroduced or transplanted. The transplanted cells then reestablish the blood cell production process in the bone marrow. The healthy stem cells may come from the blood or bone marrow of a related or unrelated donor. If patients do not have a matched related donor, doctors do not know what the next best donor choice is or if a haplo related donor or MUD is better. This trial may help researchers understand whether a haplo related donor or a MUD HCT for children with acute leukemia or MDS is better or if there is no difference at all.

Eligible Conditions
  • Stem Cell Transplantation
  • Acute Leukemia
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndrome

Treatment Effectiveness

Study Objectives

4 Primary · 6 Secondary · Reporting Duration: 0.5, 1, and 2 year post HCT

Year 2
Cumulative incidences of mild, moderate, and severe chronic graft versus host disease (cGVHD)
Therapeutic procedure
Year 2
Evaluate the influence of potential risk factors at baseline on primary and secondary graft failure, OS, DFS, GRFS, relapse, aGVHD and cGVHD
Evaluate the influence of potential risk factors at baseline on primary and secondary graft failure, OS, DFS, GRFS, relapse, aGVHD and cGVHD at 1 and 2 years after haplo and MUD HCT.
1 year post HCT
Hematocrit procedure
Cytomegalovirus Infections
1 year post-transplant.
Compare the post HCT outcomes (primary and secondary graft rejection, graft failure, OS, DFS, GRFS, NRM, relapse, GvHD) by subject race/ethnicity, area-based SES, area-based annual household income and primary spoken language.
HRQoL outcomes in racial/ethnic minorities and compare HRQoL outcomes between White patients receiving haploHCT and racial/ethnic minority patients receiving haploHCT
Year 1
Hemopoietic stem cell transplant
12 weeks post randomization
DFS from randomization
Hemopoietic stem cell transplant
12-18 months post-HSCT
Vaccination
Year 2
Cumulative incidence of mild, moderate, and severe chronic graft versus host disease (cGVHD)
Cumulative incidence of relapse
Cumulative incidence of transplant related mortality (TRM)
Year 2
Generic PedsQLTM: Compare differences in health-related quality of life (HRQOL) between haploHCT and MUD HCT at 6-month, 1 year and 2 years post-transplant.
PedsQLTM Stem Cell Transplant: Compare differences in health-related quality of life (HRQOL) between haploHCT and MUD HCT at 6-month, 1 year and 2 years post-transplant.
60 days post transplant
Primary and secondary graft failure
Year 1
Incidence of viremia with or without end organ disease
Year 1
Incidence of any significant fungal infections
Day 100
Incidence of sinusoidal obstruction syndrome (SOS)
Incidence of transplant-associated thrombotic microangiopathy (TA-TMA)
Day 365
Pace of reconstitution of T, B, and natural killer (NK) cells and immunoglobulins
Day 365
Pace of reconstitution of T, B, and NK cells and immunoglobulins
Year 2
Incidence of "imminent" relapses, treatments administered, and progression to relapse
The impact of graft composition on GvHD, relapse, and viremia
Year 2
Summary score from the Generic Pediatric Quality of Life Inventory (PedsQL) (excluding School Functioning)
Summary score from the PedsQL Stem Cell Transplant module
Between 12-18 months post-HSCT
Vaccination
Year 1
Graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) after haploHCT and MUD HCT
Day 180
Acute graft versus host disease (aGVHD) Grades II-IV and III-IV
Day 100
Cumulative incidences of neutrophil engraftment
Cumulative incidences of platelet engraftment
Year 5
Overall survival (OS)
Year 5
Disease free survival (DFS)
Year 1
Cumulative incidence of severe GVHD
Year 1
Cumulative incidence of severe graft versus host disease (GVHD)
Year 1
DFS and severe GVHD outcomes
HRQoL outcomes in racial/ethnic minorities

Trial Safety

Trial Design

6 Treatment Groups

ARM C: nonrandomized haploHCT
1 of 6
Arm A: haploHCT
1 of 6
Arm B: MUD-HCT
1 of 6
Arm B (MUD-HCT)
1 of 6
Arm A (halploHCT)
1 of 6
Arm C (haploHCT)
1 of 6

Experimental Treatment

435 Total Participants · 6 Treatment Groups

Primary Treatment: ARM C: nonrandomized haploHCT · No Placebo Group · Phase 3

ARM C: nonrandomized haploHCT
Procedure
Experimental Group · 1 Intervention: Haploidentical hematopoietic cell transplantation (haploHCT) · Intervention Types: Procedure
Arm A: haploHCT
Procedure
Experimental Group · 1 Intervention: Haploidentical hematopoietic cell transplantation (haploHCT) · Intervention Types: Procedure
Arm B: MUD-HCT
Procedure
Experimental Group · 1 Intervention: matched unrelated donor hematopoietic cell transplantation (MUD-HCT) · Intervention Types: Procedure
Arm B (MUD-HCT)Experimental Group · 17 Interventions: Echocardiography, Lumbar Puncture, Multigated Acquisition Scan, Biospecimen Collection, Bone Marrow Aspiration, Busulfan, Total-Body Irradiation, Tacrolimus, Methotrexate, Fludarabine, Myeloablative Conditioning, Cyclophosphamide, Thiotepa, Matched Unrelated Donor Hematopoietic Cell Transplantation, Questionnaire Administration, Lapine T-Lymphocyte Immune Globulin, Quality-of-Life Assessment · Intervention Types: Procedure, Procedure, Procedure, Procedure, Procedure, Drug, Radiation, Drug, Drug, Drug, Procedure, Drug, Drug, Procedure, Other, Biological, Other
Arm A (halploHCT)Experimental Group · 20 Interventions: Echocardiography, Lumbar Puncture, Multigated Acquisition Scan, Biospecimen Collection, Bone Marrow Aspiration, Busulfan, Melphalan, Total-Body Irradiation, Tacrolimus, Haploidentical Hematopoietic Cell Transplantation, Fludarabine, Myeloablative Conditioning, Cyclophosphamide, Thiotepa, Mycophenolate Mofetil, T-Cell Depletion Therapy, Rituximab, Questionnaire Administration, Lapine T-Lymphocyte Immune Globulin, Quality-of-Life Assessment · Intervention Types: Procedure, Procedure, Procedure, Procedure, Procedure, Drug, Drug, Radiation, Drug, Procedure, Drug, Procedure, Drug, Drug, Drug, Procedure, Biological, Other, Biological, Other
Arm C (haploHCT)Experimental Group · 20 Interventions: Echocardiography, Lumbar Puncture, Multigated Acquisition Scan, Biospecimen Collection, Bone Marrow Aspiration, Busulfan, Melphalan, Total-Body Irradiation, Tacrolimus, Haploidentical Hematopoietic Cell Transplantation, Fludarabine, Myeloablative Conditioning, Cyclophosphamide, Thiotepa, Mycophenolate Mofetil, T-Cell Depletion Therapy, Rituximab, Questionnaire Administration, Lapine T-Lymphocyte Immune Globulin, Quality-of-Life Assessment · Intervention Types: Procedure, Procedure, Procedure, Procedure, Procedure, Drug, Drug, Radiation, Drug, Procedure, Drug, Procedure, Drug, Drug, Drug, Procedure, Biological, Other, Biological, Other
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Echocardiography
2013
Completed Phase 4
~11830
Lumbar Puncture
2006
Completed Phase 2
~210
Biospecimen Collection
2004
Completed Phase 1
~670
Bone Marrow Aspiration
2011
Completed Phase 2
~1730
Busulfan
2008
Completed Phase 3
~1110
Melphalan
2008
Completed Phase 3
~1750
Total-Body Irradiation
1997
Completed Phase 3
~1220
Tacrolimus
2011
Completed Phase 4
~4510
Methotrexate
2013
Completed Phase 4
~3710
Fludarabine
2012
Completed Phase 3
~1170
Cyclophosphamide
1995
Completed Phase 3
~3930
Thiotepa
2008
Completed Phase 3
~2570
Mycophenolate Mofetil
1997
Completed Phase 4
~2330
Rituximab
1999
Completed Phase 4
~1880

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: 0.5, 1, and 2 year post hct

Who is running the clinical trial?

Children's Oncology GroupLead Sponsor
447 Previous Clinical Trials
235,775 Total Patients Enrolled
Heather J SymonsPrincipal InvestigatorChildren's Oncology Group

Eligibility Criteria

Age 6 - 22 · All Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
You are aged between 6 months and 22 years at enrollment.
There is no HLA-matched sibling donor available for stem cell donation.
You possess a haploidentical family donor confirmed by intermediate resolution HLA typing.
Individuals without a suitable MUD contributor are qualified to enter Arm C.
You must abide by all regulations set forth by the FDA and NCI for human studies.
You are enrolled in other studies.
You have been diagnosed with ALL, AML, or MDS for which an allogeneic hematopoietic stem cell transplant is indicated and you are to be confirmed in complete remission status prior to initiating the HCT treatment plan.
You have not had a prior allogeneic hematopoietic stem cell transplant.
Patients with a confirmed 8/8 MUD adult donor, verified through high resolution HLA typing, may be randomized to Arm A or Arm B.
All patients and/or their guardians must provide a written consent affirming knowledge of the information.