Phase 2 N=76 Randomized Treatment

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

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

Bottom Line

View on ClinicalTrials.gov: NCT01338987 ↗

Enrolled (actual)

Serious AEs

42.3%

Results posted

Apr 2019

Primary outcome: Primary: Percentage of B Cells at One Year Post-transplant in Participants Who Did/Did Not Receive Leuprolide Following Bone Marrow Transplant (BMT) — 22.1; 21.9; 14.3 percentage of cells

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: First Allogeneic Bone Marrow Transplant (BMT) (Procedure); Leuprolide (Drug); 18F FLT (Drug); Cyclophosphamide (Drug); Methotrexate (Drug); Tacrolimus (Drug); Total Body Irradiation (Radiation); Busulfan (Drug); Fludarabine (Drug); Second Allogeneic Bone Marrow Transplantation (Procedure)
Age: Pediatric, Adult · 4+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of B Cells at One Year Post-transplant in Participants Who Did/Did Not Receive Leuprolide Following Bone Marrow Transplant (BMT)	22.1; 21.9; 14.3	—
PRIMARY Time to Engraftment in First Transplant Recipients Only With Median Thoracic Spine Standardized Uptake Values (SUV) of 1.4 or Greater Than Those Patients With SUV's Less Than 1.4	5; 15	0.0075 sig
PRIMARY Number of Adverse Events Related to Study Drug Experienced by Participants After Second Bone Marrow Transplant (BMT)	—	—
SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	10; 8; 20; 4; 2	—

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.

Eligibility Criteria

ELIGIBILITY CRITERIA:

INCLUSION CRITERIA: TRANSPLANT RECIPIENT

At National Institutes of Health (NIH). Age greater than or equal to 15 years old and/or greater than or equal to 9 years old and pubertal and less than or equal to 55 years for recipient. Pubertal is defined by: prior menses at any time (females), documentation of clinical Tanner stage greater than 2 at some point pre-chemotherapy or at the current visit. (At this point, sex steroids have been produced for a few years which have driven initial pubertal development). Tanner 2 is defined as: breast buds for females with coarse pubic hair, and coarse pubic hair and testes > 2.5cm for males.
At Children's National Medical Center only: age > 4 years old and 30,000 for B-cell ALL and >100,000 for T-cell ALL) at diagnosis
Persistence of minimal residual disease despite induction chemotherapy

Pediatric ( 25% with greater 200 cells counted) marrow at day 29), M2 (5-25% blasts with greater than 200 cells counted) bone marrow or minimal residual disease (MRD) > 1% at day 29 who then fail at day 43 with either an M2 or M3 BM or MRD > 1%

Persistent leukemia and t(9;22) (MRD >1% day 29 or MRD > 0.01% end consolidation)
11q23 (MLL) rearrangements detected by cytogenetic or polymerase chain reaction (PCR) at initial diagnosis who are slow early responders (M2/M3 at day 14 or MRD> 0.01% at day 29)
Extreme hypodiploidy ( 2 abnormalities)
inv (3) or t (3;3); t(11;19)(q23;p13.1); +13; -17/17p-; -18; -20; (t(6;9); t(6;11); -7, 7q-; -5, 5q-; trisomy 8; t(3;5); t(9:11)(p22q23)
monosomy karyotype (presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality.
Any other karyotype EXCEPT t(8;21), t(9;11), inv(16), or t (16;16), and M3 (17; 17) unless ckit mutation present and then eligible.
AML emerging from CML (blast crisis) are eligible

-Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy

Secondary AML, defined as AML related to antecedent myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), or cytotoxic chemotherapy
Hyperleukocytosis (White blood cell (WBC) > 100,000 at diagnosis)
Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene (FLT3-LM; FLT-ITDs)
Bilineage or biphenotypic leukemias are high risk features and eligible.

Pediatric ( 15% after first course of chemotherapy)

Complex karyotype, monosomy 7, or -5/-5q, FLT3 ITD-AR (>0.4) EXCEPT if also inv(16)/t(16;16), t(8,21)
Normal cytogenetics or abnormal cytogenetics EXCEPT if also inv(16)/t(16;16), t(8,21) are eligible for SIBLING transplant only
Bilineage or biphenotypic leukemias are high risk features and eligible.

4.3. Myelodysplastic Syndrome Refractory Anemia with Excess Blasts (RAEB) 1 or 2; cytogenetics showing complex karyotype (3 or more abnormalities), monosomy 7/del(7q), or inv(3)/t(3q)/del(3q); or transfusion dependent.

4.4. Chronic Myelomonocytic Leukemia

4.5. Chronic Myelogenous Leukemia who have failed 2G- tyrosine kinase inhibitors (TKI)

4.6. Standard pediatric indications for myeloablative transplantation for patients undergoing bone marrow transplant at Children's National Medical Center per institutional guidelines

Disease status

If patients are found to not be in remission at screening, then the patient may be returned to their primary hematologist/oncologist or may receive chemotherapy as per standard of care for the malignant disease. Patients for whom this would be their first allogeneic transplant must be in remission ( 60 ml/min/1.73 m(2). Glomerular filtration rate (GFR) may also demonstrate adequate renal function.

Left ventricular ejection fraction greater than or equal to 50% OR shortening fraction of greater than or equal to 27% demonstrated on 2-dimension (2D) echocardiogram or multi-gated acquisition scan (MUGA).
Pulmonary function of Diffusing Capacity of the Lung for Carbon Monoxide (DLC0) adj/alveolar volume (VA) and

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01338987). 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.