Pilot Study of Lupron to Improve Immune Function After Allogeneic Bone Marrow Transplantation
- One way to treat certain cancers of the blood and immune system is to give a patient stem cells from the bone marrow of a donor whose genes are very similar but not identical to the patient s. One problem with these transplants is that the new immune cells may not work as well in the recipient as they did in the donor. The result may be that the immune system will not work as well. This can increase the risk of severe infections and other complications.
- Researchers are studying the use of drugs that lower hormone levels and may allow the immune system to recover in a way that improves white blood cell function. In this study they will be looking at the drug lupron, a drug that lowers estrogen or testosterone levels, to see if it might improve the function of the newly transplanted cells.
- To determine whether lupron improves immune system function after bone marrow transplantation from a donor with similarities in their immune cells (matched to each other).
- To evaluate the effectiveness of a nuclear medicine test with a radiotracer drug FLT in imaging studies. FLT will be used to image the immune system function in patients who have received bone marrow from the donor.
- People between 15 (or as young as 9 in those who have gone through puberty) and 40 years of age. These patients must have acute myelogenous leukemia, acute lymphocytic leukemia, or high-risk myelodysplastic syndrome. They must also be eligible for a bone marrow transplant.
- Genetically similar donors for the patients who are eligible for a transplant.
- People taking part in the study will be screened with a physical examination, medical history, blood and urine tests, and imaging studies. Patients who are not in remission or who require a bone marrow donor search may receive chemotherapy first.
- Donors will provide bone marrow for transplant according to standard bone marrow transplant (BMT) procedures.
- All women and half of the men will receive regular lupron doses 2 weeks before BMT to suppress hormone function.
- All recipients will receive 4 days of radiation followed by 2-4 days of chemotherapy before the bone marrow transplant (depending on age). Recipients will also receive other drugs to prevent transplant rejection and other complications of transplantation.
- Recipients will be monitored in the hospital for 4 weeks after transplant with blood tests and other studies.
- Some recipients will have an imaging study with FLT during the protocol. These imaging studies will take place before the transplant, on days 5 and 28 after transplant, and at a later time to be determined by the study researchers.
- Following discharge, participants will be monitored closely for up to 6 months, with regular but less frequent followup visits for at least 5 years. Study-related medications, including vaccinations for the new immune system, will be provided by the National Institutes of Health during the hospital stay and after discharge.
Myelodysplastic Syndrome RAEB 2
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Myelodysplastic Syndrome RAEB 1
Procedure: Allogeneic HSC Transplantation
Drug: 18F FLT
Radiation: Total Body Irradiation
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multi-Institutional Prospective Pilot Study of Lupron to Enhance Lymphocyte Immune Reconstitution Following Allogeneic Bone Marrow Transplantation in Post-Pubertal Children and Adults With Molecular Imaging Evaluation|
- To determine if Lupron improves B lymphocyte reconstitution after HSCT. [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: No ]
- To assess whether 18F FLT PET/CT could predict early engraftment/immune reconstitution in marrow and thymus after allogeneic HSCT. [ Time Frame: within first 2 months post-transplant ] [ Designated as safety issue: Yes ]
- To investigate whether Lupron will decrease the incidence of acute or chronic GVHD without altering GVT after allogeneic HSCT. [ Time Frame: years ] [ Designated as safety issue: No ]
- To evaluate if Lupron decreases the incidence of infections after HSCT. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1
Lupron: 30 mg intramuscular injection(for adult) or 11.25 mg (for patients & lt; 18 years) between day -13 and day -20 pre-HSCT but definitely prior to initiation of preparative regimen as a 4 month intramuscular injection for patients & gt; 18 years and as a 3 month injection (adult preparation) for patients & lt; 18 years
Active Comparator: Arm 2
Procedure: Allogeneic HSC Transplantation
Allogeneic HSC TransplantationDrug: 18F FLT
18F FLT: 0.07 mCi/kg with a maximum of 3 mCi On day + 28 (+/- 5 days)Drug: Cyclophosphamide
Cyclophosphamide: 60 mg/kg IV on days -4 and -3 (for Adults & gt; 22 years) or Cyclophosphamide: cyclophosphamide 50 mg/kg IV, Days -5, -4, -3, -2. (For Pediatric & lt; /= 22 years)Drug: Methotrexate
Methotrexate:10 mg/m2 IV on day +1, and 5 mg/m2 IV Days + 3, 6, 11Drug: Tacrolimus
Tacrolimus:0.02 mg/kg/day CIV on day -1.Radiation: Total Body Irradiation
Total Body Irradiation (TBI) 1200 cGy fractionate twice daily (lung block) Days -8, -7, -6, -5 (adult), -9, -8, -7, -6 (ped)
- Impaired lymphocyte immune reconstitution is associated with morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT).
- Data suggest that one of the limitations of immunity after HSCT is the lack of thymus recovery and proper B cell development.
- Androgen withdrawal has been shown to enhance T and B lymopoiesis.
- Lupron is an approved, safe, gonadotropin releasing hormone (GnRH) agonist/antagonist.
- Noninvasive imaging modalities to study immune reconstitution would be invaluable to predict optimal or impaired immune recovery permitting early institution of therapies.
- FLT is 3 -deoxy-3 18F-fluorothymidine, a radiolabeled thymidine analogue that illustrates dividing hematopoietic cells and may predict immune recovery after allogeneic HSCT.
- FLT has been used safely in patients who have received intensive chemotherapy.
- Primary: To determine if Lupron improves B lymphocyte reconstitution after HSCT.
- Primary: To assess whether 18F FLT PET/CT could predict early engraftment/immune reconstitution in marrow and thymus after allogeneic HSCT.
- Secondary: To investigate whether Lupron will decrease the incidence of acute or chronic GVHD without altering GVT after allogeneic HSCT.
- Secondary: To evaluate if Lupron decreases the incidence of infections after HSCT.
- Secondary: To evaluate if Lupron improves de novo lymphocyte immune reconstitution, using T cell receptor excision circles (TREC), spectrotype, and peripheral total T cell subset numbers as measurements of T cell reconstitution after HSCT.
- Secondary: To evaluate the safety of 18F FLT in the peri-transplant period.
Patients > 9 years old and pubertal and/or > 15 year and less than 55 years with aggressive leukemia (Acute Myelogenous Leukemia (AML), myelodysplastic syndromes (MDS) with high risk cytogenetics, Acute Lymphocytic Leukemia (ALL), CMML, certain CML) requiring HSCT.
- This is a prospective pilot study, the primary aims of which are to assess whether Lupron enhances lymphocyte recovery after HSCT and whether FLT imaging can be used to predict engraftment/immune reconstitution.
- Post-pubertal pediatric male patients (< 18 years) will be randomized to receive a 3 month (11.25 mg) injection and adult male patients will be randomized to receive 4-month preparation of Lupron (30 mg) or placebo two weeks before the preparative regimen. Women will receive Lupron at the proper dose per age and be evaluated in the treated cohort.
- A target of 64 evaluable patients will be enrolled on this trial, which may necessitate up to 118 patients enrolled to reach this target.
- The planned length of this trial is 5 years with interim analyses at day 100 and day 365.
- 23 of these patients will be evaluated using FLT. They will undergo FLT PET/CT imaging on day -1, at day +5 or day +9, at 4 weeks, and at a future point to include evidence of GVHD relapse, or immune recovery. Initial images will be correlated with engraftment.
- Study endpoints to include: 1)safety of Lupron in the context of allogeneic BMT, 2) lymphocyte reconstitution after Lupron administration, 3) the incidence of acute and chronic GVHD and infectious complications, 4) remission rates after HSCT
Please refer to this study by its ClinicalTrials.gov identifier: NCT01338987
|Contact: Zetta A Blacklock-Schuver, R.N.||(301) email@example.com|
|Contact: Ronald E Gress, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, Oklahoma|
|University of Oklahoma||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Principal Investigator:||Ronald E Gress, M.D.||National Cancer Institute (NCI)|