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

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ClinicalTrials.gov Identifier: NCT01338987
Recruitment Status : Active, not recruiting
First Posted : April 20, 2011
Last Update Posted : December 11, 2017
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


  • 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome RAEB 2 Acute Lymphocytic Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome RAEB 1 Procedure: Allogeneic HSC Transplantation Drug: Lupron Drug: 18F FLT Drug: Cyclophosphamide Drug: Methotrexate Drug: Tacrolimus Radiation: Total Body Irradiation Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 19, 2011
Estimated Primary Completion Date : November 19, 2020
Estimated Study Completion Date : November 19, 2020

Arm Intervention/treatment
Active Comparator: Arm 1
Lupron Arm
Drug: Lupron
Lupron: 30 mg intramuscular injection(for adult) or 11.25 mg (for patients <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 > 18 years and as a 3 month injection (adult preparation) for patients < 18 years
Active Comparator: Arm 2
Procedure: Allogeneic HSC Transplantation
Allogeneic HSC Transplantation
Drug: 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 > 22 years) or Cyclophosphamide: cyclophosphamide 50 mg/kg IV, Days -5, -4, -3, -2. (For Pediatric </= 22 years)
Drug: Methotrexate
Methotrexate:10 mg/m2 IV on day +1, and 5 mg/m2 IV Days + 3, 6, 11
Drug: 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)

Primary Outcome Measures :
  1. To determine if Lupron improves B lymphocyte reconstitution after HSCT. [ Time Frame: 12 months post-transplant ]
  2. 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 ]
  3. To assess safety of Lupron after 2nd HSCT and evaluate whetherFLT can predict relapse [ Time Frame: 12 months after second BMT ]

Secondary Outcome Measures :
  1. To investigate whether Lupron will decrease the incidence of acute or chronic GVHD without altering GVT after allogeneic HSCT. [ Time Frame: years ]
  2. To evaluate if Lupron decreases the incidence of infections after HSCT. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   9 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. At 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.
  2. At Children s National Medical Center only: age > 4 years old and < 24.
  3. At University of Oklahoma: Age greater than or equal to 17 years old and less than or equal to 55 years for recipient.
  4. A diagnosis of a hematologic malignancy for which stem cell transplant is standard of care:

4.1. Acute Lymphocytic Leukemia

Adult: (greater than or equal to 22 years) greater than or equal to CR2 OR CR1 with:

  • Matched sibling donor for recipient treated on adult leukemia regimen
  • t(9:22) or bcr-abl+; t(4:11), t(1:19), t(8:14), 11q23 (MLL rearrangements) complex cytogenetics (5 or more chromosomal abnormalities), hypodiploidy (<44 chromosomes). Note that patients with ALL blast crisis who emerge from CML are also eligible
  • Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy
  • High WBC (>30,000 for B-cell ALL and >100,000 for T-cell ALL) at diagnosis
  • Persistence of minimal residual disease despite induction chemotherapy

Pediatric (< 22 years): greater than or equal to CR2 OR CR1 with high risk features

  • Matched sibling donor for recipient treated on adult leukemia regimen
  • Primary induction failure (M3 (>25% with greater 200 cells counted) marrow at day 29), M2 (5-25% blasts with greater than 200 cells counted) bone marrow or 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% endconsolidation)
  • 11q23 (MLL) rearrangements detected by cytogenetic or PCR at initial diagnosis who are slow early responders (M2/M3 at day 14 or MRD> 0.01% at day 29)
  • Extreme hypodiploidy (< 44 chromosomes or DNA index of <0.81) detected by cytogenetic/ploidy analysis

4.2 Acute Myelogenous Leukemia

Adult: (greater than or equal to 22 years) greater than or equal to CR2 OR CR1 with high one of the following risk features

-Adverse or intermediate-risk cytogenetics including:

  1. Normal cytogenetics
  2. complex karytoype (>2 abnormalities)
  3. 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)
  4. monosomy karyotype (presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality.
  5. 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.
  6. 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 MDS, MPN, or cytotoxic chemotherapy
    • Hyperleukocytosis (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 (< 22 years): greater than or equal to CR2 OR CR1 with a high risk feature including:

    -Primary induction failure (greater than or equal to 5% blasts in marrow after induction)

    • Persistent leukemia (>15% after first course of chemotherapy)
    • Complex karyoptype, 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 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 HSCT at Children s National Medical Center per institutional guidelines

    5. 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 (< 5% malignant blasts in marrow and peripheral blood and no evidence of extramedullary disease) for transplant. Patients enrolled on this protocol for their second transplant do not need to have attained remission prior to transplant.

    6. Performance status: Karnofsky or Lansky performance status greater than or equal to 60% AND life expectance of greater than 3 months.

    7. Ability to give informed consent. For recipients and donors < 18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in an age appropriate discussion in accordance with institutional guidelines.

    8 Hepatic function: Patients must have evidence of adequate liver function prior to enrollment defined by total bilirubin < 2.5 mg/dL (unless documented Gilbert s syndrome) AND transaminases less than or equal to 5 x the upper limit of normal for age appropriate indices.

    9. Renal function: Patients must have evidence of adequate renal function to proceed with stem cell transplant, creatinine clearance > 60 ml/min/1.73 m2. GFR may also demonstrate adequate renal function.

    10. Left ventricular ejection fraction greater than or equal to 50% OR shortening fraction of greater than or equal to 27% demonstrated on 2D echocardiogram or MUGA.

    11. Pulmonary function of DLC0 adj/VA and FEV1 greater than or equal to 60% of normal indices for age and height unless the patient has a likely acute reversible etiology of decline and then DLCO adj/VA greater than or equal to 30% of normal. Pediatric patients unable to complete PFTs may be enrolled as per enrolling institution SOP for recipient guidelines.

    12. Patients with prior autologous stem cell transplants will be included. Patients with prior allogeneic stem cell transplants will be eligible for 2nd BMT if not previously transplanted with FLT on 11-c-0136.

    13. Prior experimental systemic therapies must have been completed greater than 2 weeks prior to study entry.


    1. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
    2. Active infections not responding to therapy. All efforts should be made to clear the infection prior to enrollment.
    3. Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment PI or AI would render the patient unlikely to tolerate the protocol therapy or complete the study.
    4. Presence of active malignancy from an organ system other than hematopoietic.
    5. HIV infection.
    6. Chronic active hepatitis B infection. Patients may be hepatitis B core antibody positive but must be surface antigen negative and without active evidence of disease.
    7. Pregnant or lactating females will be excluded from this trial due to unknown risks to the developing fetus. Patients of child-bearing potential must use an effective form of contraception while on study.
    8. Sexually active individuals capable of becoming pregnant who are unable or unwilling to use effective form(s) of contraception during time enrolled on study and for 1 year post-transplant.
    9. History of prior Lupron intolerance. Note: patients ARE eligible if prior or current lupron exposure.


    1. Age greater than or equal to 2 and less than or equal to 60 years old and able to give consent or assent. For donors < 18 years old, the legal guardian must be able to provide informed consent and an evaluation by a LSW or psychiatric personnel will be needed to determine willingness to participate. Pediatric patients will be included in an age appropriate discussion in accordance with institutional guidelines.
    2. HLA-matched related donor, excluding identical twins. Donors must be matched at least 7 loci out of 8 at the allele or antigen level excluding antigen DRB1 mismatch.
    3. Donor selection will be in accordance with NIH/CC Department of Transfusion Medicine criteria and must be able to medically endure stem cell collection or as per local institutional guidelines.
    4. Donors must be HIV negative, HTLV negative, HBsA negative.
    5. Donors must be physically able to and willing to tolerate marrow harvest collection preferably, or in the absence of this option, able and willing to donate via peripheral blood pheresis.


    1. History of medical illness that in the estimation of the PI or DTM physician precludes donation of marrow.
    2. Anemia (Hb < 10 gm/dl) or thrombocytopenia (< 100,000/ ul).
    3. Pregnant females (due to risk to fetus).
    4. Current psychiatric diagnosis that would compromise compliance with transplant protocol or precludes appropriate informed consent.
    5. Presence of any blood transmissible infectious disease that cannot be cleared prior to stem cell collection and poses an unacceptable risk for the recipient (excludes CMV).
    6. Active malignancy will exclude the donor. Any malignancy less than five years postremission will exclude the donor. Non-hematologic malignancies greater than 5 years ago will not exclude the donor. Any history of hematologic malignancy will be considered on a case by case basis.
    7. Any medical contraindication to anesthesia or marrow donation will exclude the donor.
    8. Donors receiving experimental therapy or investigational agents.
    9. Active autoimmune disease that in the opinion of the PI or AI would compromise the success of the transplant.


    1. Unrelated donor matched at HLA-A, B, C, and DR loci by high resolution typing (at 8/8 or 7/8 antigen/allele match) are acceptable donors.
    2. The evaluation of donors shall be in accordance with existing National Marrow Donor Program (NMDP) Standard Policies and Procedures at all institutions.


    1. Meets criteria for Transplant Recipient
    2. Age greater than or equal to 18 years old at NCI, and age > 4 years and < 24 years at Children s National Medical Center
    3. Donor who is willing to undergo bone marrow or stem cell harvest.


    1. History of prior fluorothymidine allergy or intolerance.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01338987

United States, District of Columbia
Childrens National Medical Center
Washington, District of Columbia, United States
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Christopher G Kanakry, M.D. National Cancer Institute (NCI)

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01338987     History of Changes
Other Study ID Numbers: 110136
First Posted: April 20, 2011    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: August 17, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Thymic Renewal
Stem Cell Transplant
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Myelodyplastic Syndrome

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fertility Agents, Female
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating