Phase 2
N=89
Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System
Myelodysplastic Syndrome · Hodgkin's Lymphoma · Non-Hodgkin's Disease · Acute Leukemia · Multiple Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT00520130 ↗Enrolled (actual)
89
Serious AEs
86.5%
Results posted
Aug 2017
Primary outcome: Primary: Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD) — 42; 38 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Rituximab (Biological); Cyclosporine (Drug); Allogenic stem cell transplant (ASCT) (Drug); Conditioning Chemotherapy (Drug); TMS (Drug); FLAG (Drug); EPOCH-F (Drug); Alemtuzumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD) |
42; 38 | — |
| PRIMARY Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD) |
50; 12; 28; 5 | — |
| PRIMARY Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells |
24; 1; 22; 7; 20; 25 | — |
| PRIMARY Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells |
20; 3; 17; 6; 16; 6 | — |
| PRIMARY Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire |
48; 90; 31; 66; 35; 75 | — |
| PRIMARY Changes in CD8 T Cell Receptor Vbeta Repertoire |
62; 78; 54; 81; 62; 84 | — |
| SECONDARY Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD) |
13; 21 | — |
| SECONDARY Toxicities |
43; 42 | — |
| SECONDARY Days to Engraftment of Neutrophils |
11; 9 | — |
| SECONDARY Days to Engraftment of Platelets |
19; 14 | — |
| SECONDARY Days to Engraftment of Lymphocytes |
16; 76 | — |
| SECONDARY Overall Survival |
41.7; 18.8 | — |
| SECONDARY Early Treatment Related Mortality |
1; 0 | — |
| SECONDARY Percentage of Participants With Late Treatment Related Mortality |
28; 29 | — |
| SECONDARY Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant |
— | — |
| SECONDARY Immune Reconstitution of Normal Killer (NK) Cells |
123; 15; 270; 31; 134; 124 | — |
| SECONDARY Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations |
171; 0; 285; 21; 297; 61 | — |
| SECONDARY Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations |
72; 1; 204; 6; 334; 54 | — |
Summary
Background:
Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without a human leukocyte-antigen (HLA) tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patients immune system attacks the transplanted donor cells.
This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.
Objectives:
To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.
To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.
Eligibility:
People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.
Design:
All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.
All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.
Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:
* Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
* Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.
Patients receive the donors stem cells and immune cells 2 days after completing the conditioning regimen.
Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.
A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.
...
Eligibility Criteria
- ELIGIBILITY CRITERIA RECIPIENT ON STANDARD CARE THERAPY:
- The patient is 18-74 years of age.
- The patient has a potentially suitable 8/8 donor if they are between the ages of 69-74 years of age or a potentially suitable 8/8 or 7/8 unrelated donor(s) in the National Marrow Registry or Other Available Registry if they are between the ages of 18-74.
- The patient currently does not meet the protocol s eligibility/enrollment criteria for any reason.
- There is a high likelihood that the patient, in the opinion of the principal investigator (PI) or lead associate investigator (LAI), will meet the protocols eligibility/enrollment criteria to proceed to transplant after standard therapy is completed.
- The patient or legal guardian is able to give informed consent.
EXCLUSION CRITERIA RECIPIENT ON STANDARD CARE THERAPY:
- Human immunodeficiency virus (HIV) infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
- Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.
Data sourced from ClinicalTrials.gov (NCT00520130). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.