Pilot Study of Leuprolide to Improve Immune Function After Allogeneic Bone Marrow Transplantation

Summary

Background:

* 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 patients. 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 leuprolide, a drug that lowers estrogen or testosterone levels, to see if it might improve the function of the newly transplanted cells.

Objectives:

* To determine whether leuprolide improves immune system function after bone marrow transplant 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 3-deoxy-3 18F-fluorothymidine (FLT) in imaging studies. FLT will be used to image the immune system function in patients who have received bone marrow from the donor.

Eligibility:

* People between 15 (or as young as 9 in those who have gone through puberty) and 55 years of age. These patients must have acute myelogenous leukemia, acute lymphocytic leukemia, high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or chronic myeloid leukemia. They must also be eligible for a bone marrow transplant.
* Genetically similar donors for the patients who are eligible for a transplant.

Design:

* 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 leuprolide 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.

Conditions

• Myelodysplastic Syndrome
• Acute Lymphocytic Leukemia
• Acute Myelogenous Leukemia
• Chronic Myelogenous Leukemia
• Chronic Myelomonocytic Leukemia

Interventions

PROCEDURE

First Allogeneic Bone Marrow Transplant (BMT)

First Allogeneic Bone Marrow Transplant

DRUG

Leuprolide

Leuprolide: 30 mg intramuscular injection(for adult) or 11.25 mg (for patients \<18 years) between day -13 and day -20 pre-bone marrow transplant but definitely prior to initiation of preparative regimen as a 4 month intramuscular injection for patients \> 18 years and as a 3 month injection (adult preparation) for patients \< 18 years

DRUG

18F FLT

For the first 23 patients undergoing 1st bone marrow transplant (BMT):\[18F\]fluorothymidine (18F FLT): 0.07 mCi/kg with a maximum of 3 mCi On day + 28 (+/- 5 days) For 2nd BMT: 18F FLT: 0.07 mCi/kg with a maximum of 3 mCi On day -1, + 28, day 60 and at relapse (+/- 5 days)

DRUG

Cyclophosphamide

Cyclophosphamide: 60 mg/kg intravenous (IV) on days -4 and -3 (for Adults \> 22 years) or Cyclophosphamide: cyclophosphamide 50 mg/kg IV, Days -5, -4, -3, -2. (For Pediatric \</= 22 years)

DRUG

Methotrexate

Methotrexate:10 mg/m(2) intravenous (IV) on day +1, and 5 mg/m(2) IV Days + 3, 6, 11

DRUG

Tacrolimus

Tacrolimus:0.02 mg/kg/day continuous intravenous infusion (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)

DRUG

Busulfan

Second choice is Busulfan (with goal steady state of 800-1000) with fludarabine or cyclophosphamide at myeloablative dosing or non-myeloablative dosing.

DRUG

Fludarabine

Given with Busulfan as alternative to cyclophosphamide in second transplant setting only

PROCEDURE

Second Allogeneic Bone Marrow Transplantation

Second Allogeneic Bone Marrow Transplantation

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Christopher G Kanakry, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-04-19

Primary Completion

2017-12-01

Completion

2020-11-19

FDA Drug

Yes

Countries

• United States

Study Locations