Allogeneic HSCT for Peripheral Blood Stem Cell Transplantation

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
National Institutes of Health Clinical Center, Bethesda, MD
Peripheral Blood Stem Cell Transplantation+2 More
Allogeneic HSCT - Procedure
Eligibility
Any Age
All Sexes
What conditions do you have?
Select

Study Summary

Background: Blood cancers (such as leukemias or lymphomas) often do not respond to standard treatments. A transplant of blood stem cells from a healthy donor can help people with these cancers. Sometimes these transplants cause serious side effects, including a common immunologic problem called graft-versus-host disease. A drug called cyclophosphamide given early after the transplant (post-transplantation cyclophosphamide, PTCy) can reduce these complications. But sometimes this drug has its own negative effects. Furthermore, studies in mice suggest that an intermediate, rather than very high, dose of this drug may best protect against graft-versus-host disease. Objective: To find out if a lower dose of PTCy is more helpful for people who undergo blood stem cell transplants. Eligibility: People aged 18 and older who have a blood cancer and are eligible for a transplant of blood stem cells from another person. Healthy donors are also needed but must be related to the individual needing the transplant. Design: Participants will undergo screening. Transplant recipients will have imaging scans and tests of their heart and lung function. They will be assessed for the status of their cancer, including bone marrow taken from their pelvis and possibly also scans and/or fluid drawn from the spine depending on the disease type. Donors will be screened for general health. They will give several tubes of blood. They will give an oral swab and saliva and stool samples for research. Recipients will be in the hospital at least 4 to 6 weeks. They will have a temporary catheter inserted into a vein in the chest or neck. Medications will be given and blood will be drawn through the catheter. The transplanted stem cells will be given through the catheter. Participants will receive medications both before and after the transplant. Participants will return to the clinic at least once a week for 3 months after leaving the hospital. Follow-up visits will continue periodically for 5 years.

Eligible Conditions

  • Peripheral Blood Stem Cell Transplantation
  • Hematopoietic stem cells

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

2 Primary · 9 Secondary · Reporting Duration: 1 year

1 year
Describe and characterize cytokine release syndrome (CRS) (Phase I and II)
Estimate incidence progression/relapse at one year (Phase II only)
Estimate non-relapse mortality at one year (Phase II only)
Estimate overall survival and progression-free survival at one year (Phase II only)
Estimate rates of any chronic GVHD and moderate/severe chronic GVHD at one year (Phase I and II)
Phase II: Evaluate the efficacy of PTCy, at the lowest dose determined for each HLA-matching arm from phase I, as assessed by 1-year GVHD-free relapse-free survival (GRFS) rate.
100 days
Estimate rates of CMV reactivation requiring preemptive therapy. (Phase I and II)
Estimate rates of Grade II-IV and III-IV acute GVHD at 100 days (Phase I and II)
Estimate rates of symptomatic BK virus cystitis. (Phase I and II)
60 days
Phase I: Determine the lowest effective dose of PTCy in combination with sirolimus and mycophenolate mofetil as GVHD prophylaxis after reduced intensity conditioning and PBSCT, as assessed by primary graft failure AND Grade III-IV acute GVHD as ...
Day 28
Estimate rates of hematopoietic recovery/engraftment. (Phase I and II)

Trial Safety

Safety Progress

1 of 3

Trial Design

8 Treatment Groups

Donors (Haplo HCT)
1 of 8
Donors (Matched HCT)
1 of 8
Phase II Efficacy (Matched HCT)
1 of 8
Phase I Dose De-escalation (Haplo HCT)
1 of 8
Phase I Pilot for Comparative Data (Haplo HCT)
1 of 8
Phase I Dose De-escalation (Matched HCT)
1 of 8
Phase II Efficacy (Haplo HCT)
1 of 8
Phase I Pilot for Comparative Data (Matched HCT)
1 of 8
Active Control
Experimental Treatment

220 Total Participants · 8 Treatment Groups

Primary Treatment: Allogeneic HSCT · No Placebo Group · Phase 1 & 2

Phase II Efficacy (Matched HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Phase I Dose De-escalation (Haplo HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Phase I Pilot for Comparative Data (Haplo HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Phase I Dose De-escalation (Matched HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Phase II Efficacy (Haplo HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Phase I Pilot for Comparative Data (Matched HCT)Experimental Group · 7 Interventions: Melphalan, Cyclophosphamide, Sirolimus, Total Body Irradiation (TBI), Mycophenolate Mofeti, Fludarabine, Allogeneic HSCT · Intervention Types: Drug, Drug, Drug, Radiation, Drug, Drug, Procedure
Donors (Haplo HCT)NoIntervention Group · 1 Intervention: Donors (Haplo HCT) · Intervention Types:
Donors (Matched HCT)NoIntervention Group · 1 Intervention: Donors (Matched HCT) · Intervention Types:
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Melphalan
2008
Completed Phase 3
~1940
Cyclophosphamide
1995
Completed Phase 3
~4020
Sirolimus
2013
Completed Phase 4
~2750
Total Body Irradiation (TBI)
2016
Completed Phase 3
~1040
Fludarabine
2012
Completed Phase 2
~1240
Allogeneic HSCT
2015
Completed Phase 2
~60

Trial Logistics

Logistics

Participation is compensated

You will be compensated for participating in this trial.

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 1 year
Closest Location: National Institutes of Health Clinical Center · Bethesda, MD
Photo of maryland 1Photo of maryland 2Photo of maryland 3
2016First Recorded Clinical Trial
1 TrialsResearching Peripheral Blood Stem Cell Transplantation
276 CompletedClinical Trials

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
12,930 Previous Clinical Trials
41,294,240 Total Patients Enrolled
Christopher G Kanakry, M.D.Principal InvestigatorNational Cancer Institute (NCI)
4 Previous Clinical Trials
1,226 Total Patients Enrolled

Eligibility Criteria

Age Any Age · All Participants · 10 Total Inclusion Criteria

Mark “yes” if the following statements are true for you:
You have AML of intermediate or adverse risk disease by the 2017 European LeukemiaNet criteria in first morphologic complete remission (<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease).
You have AML of any risk in second or subsequent morphologic complete remission.
You have a primary myelofibrosis of intermediate-2 or higher risk by the DIPSS.
You have chronic myelomonocytic leukemia.
You have B-cell lymphoma that has relapsed within 1 year of completion of primary treatment, relapsed after autologous transplantation, or has progressed through at least 2 lines of therapy.

About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 9th, 2021

Last Reviewed: August 12th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.