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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01338987
Collaborator
(none)
76
Enrollment
3
Locations
5
Arms
115.1
Actual Duration (Months)
25.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Background:

  • Impaired lymphocyte immune reconstitution is associated with morbidity and mortality following allogeneic bone marrow transplant (BMT).

  • Data suggest that one of the limitations of immunity after BMT is the lack of thymus recovery and proper B cell development.

  • Androgen withdrawal has been shown to enhance T and B lymphopoiesis.

  • Leuprolide 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 BMT.

  • FLT has been used safely in patients who have received intensive chemotherapy.

Objectives:

  • Primary: To determine if leuprolide improves B lymphocyte reconstitution after first BMT.

  • Primary: To assess whether 18F FLT positron emission tomography (PET)/computed tomography (CT) could predict early engraftment/immune reconstitution in marrow and thymus after allogeneic BMT.

  • Primary: To assess safety of leuprolide after 2nd BMT evaluated in a separate arm.

Eligibility:

  • Patients > 9 years old and pubertal and/or >15 year and less than or equal to 55 years, with aggressive leukemia (Acute Myelogenous Leukemia (AML), myelodysplastic syndromes (MDS) with high risk cytogenetics, Acute Lymphocytic Leukemia (ALL), CMML, certain CML) requiring BMT will be enrolled at National Cancer Institute (NCI).

  • At University of Oklahoma, Age > 17 years old and less than or equal to 55 years for recipient.

  • Patients > 4 and < 24 years with the above diseases will be enrolled at Children's National Medical Center (CNMC).

Design:

  • This is a prospective pilot study, the primary aims of which are: 1) to assess whether leuprolide enhances lymphocyte recovery after first BMT, 2) whether FLT imaging can be used to predict engraftment/immune reconstitution after first transplant, and 3) whether leuprolide and FLT are tolerable for second HSCT.

  • At NCI and Univ of Oklahoma, 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 leuprolide (30 mg) or placebo two weeks before the preparative regimen for first BMT. Women and all individuals undergoing 2nd BMT will receive leuprolide at these doses per age and be evaluated in the treated cohort. At Children's National Medical Center, the patients will not receive leuprolide outside of the context of clinical care and will receive myeloablative BMT as per standard of care with FLT imaging for engraftment as the only primary endpoint.

  • A target of 68 evaluable adult patients will be enrolled on this trial, which may necessitate up to 118 patients (118 donors) enrolled to reach this target at NCI and University of Oklahoma. A total of 10 pediatric patients will be enrolled at Children's National Medical Center for FLT imaging only. Sixteen patients will be enrolled to undergo second BMT.

  • At NCI, adults greater than 18 years old both female and adult male patients undergoing 2nd BMT will receive 4-month preparation of leuprolide (30 mg) two weeks before the preparative regimen. All patients will undergo FLT imaging to evaluate whether this may predict BMT response or failure (relapse). This will be a pilot arm of 16 patients total.

  • The planned length of this trial is 7 years with interim analyses at day 100 and day

  • Some of the patients are anticipated to be evaluated using FLT (to include only patients needed for the immunological primary endpoint, not increasing total patient numbers). 23 adult NCI patients in total 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 graft-versus-host disease (GVHD) relapse, or immune recovery. An estimated 50 patients (including subset of the 23 patients undergoing serial scanning) will be imaged approximately at 1 year for evaluation of thymus reconstitution. The total possible numbers will include no more than 118 patients to achieve the 68 evaluable adults for the immunological primary endpoint. However, all 23 FLT PET/CT imaged NCI patients will undergo a single 1 year FLT for evaluation of thymus reconstitution. Up to 10 pediatric patients at CNMC will undergo FLT PET/CT imaging on Day -1, day+9, and day +28 (if possible). Initial images will be correlated with engraftment and other secondary endpoints.

Study Design

Study Type:
Interventional
Actual Enrollment :
76 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
Actual Study Start Date :
Apr 19, 2011
Actual Primary Completion Date :
Dec 1, 2017
Actual Study Completion Date :
Nov 19, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm1 First Transplt/males/leuprolide/+/-FLT Imaging

Males randomized to leuprolide for first transplant. [18F]fluorothymidine (FLT) imaging

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
Other Names:
  • Lupron

    • 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)
    Other Names:
  • [18F]fluorothymidine

    • 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)
    Other Names:
  • Cytoxan

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

    • Drug: Tacrolimus
    Tacrolimus:0.02 mg/kg/day continuous intravenous infusion (CIV) on day -1.
    Other Names:
  • Prograf

    • 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)
    Active Comparator: Arm2 First Transplt/males/No Leuprolide/+/- FLT Imaging

    Males not receiving leuprolide for first transplant [18F]fluorothymidine (FLT) imaging

    Procedure: First Allogeneic Bone Marrow Transplant (BMT)
    First Allogeneic Bone Marrow Transplant

    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)
    Other Names:
  • [18F]fluorothymidine

    • 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)
    Other Names:
  • Cytoxan

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

    • Drug: Tacrolimus
    Tacrolimus:0.02 mg/kg/day continuous intravenous infusion (CIV) on day -1.
    Other Names:
  • Prograf

    • 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)
    Experimental: Arm3 First Transplt/females/leuprolide+/- FLT Imaging

    Females receiving leuprolide for first transplant. [18F]fluorothymidine (FLT) imaging

    Procedure: First Allogeneic Bone Marrow Transplant (BMT)
    First Allogeneic Bone Marrow Transplant

    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)
    Other Names:
  • [18F]fluorothymidine

    • 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)
    Other Names:
  • Cytoxan

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

    • Drug: Tacrolimus
    Tacrolimus:0.02 mg/kg/day continuous intravenous infusion (CIV) on day -1.
    Other Names:
  • Prograf

    • 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)
    Experimental: Arm4-Second Transplt/leuprolide and FLT Imaging

    Second transplant with leuprolide and [18F]fluorothymidine (FLT) imaging

    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
    Other Names:
  • Lupron

    • 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)
    Other Names:
  • [18F]fluorothymidine

    • 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)
    Other Names:
  • Cytoxan

    • 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.
    Other Names:
  • Busulfex

    • Drug: Fludarabine
    Given with Busulfan as alternative to cyclophosphamide in second transplant setting only
    Other Names:
  • Fludara

    • Procedure: Second Allogeneic Bone Marrow Transplantation
    Second Allogeneic Bone Marrow Transplantation
    No Intervention: Healthy Volunteer - Arm 5

    Healthy Volunteer

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of B Cells at One Year Post-transplant in Participants Who Did/Did Not Receive Leuprolide Following Bone Marrow Transplant (BMT) [after first Bone Marrow Transplant, approximately 12 months post-transplant]

      B cell percentage is defined as the percentage of lymphocytes that are B cells.

    2. 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 [18F FLT scan done between days +5 to +12 and then time from that scan to engraftment measured]

      18F-FLT imaging was performed serially on patients post transplant to identify the level of uptake of 18F-FLT at a day +5 to +12 scan and the day at which neutrophils recover to >500 (i.e., subclinical bone-marrow recovery within 5 days of Bone Marrow Transplantation (BMT infusion)). On each image for each patient, the region of interest was drawn within each thoracic medullary space (n=12), generating the SUV for each space. The mean of these was calculated for each scan. The analysis was the median of the means of the SUV of the thorax values of the day 5-12 scan (averaged the SUV of the thorax for each patient and then took the medians of these).

    3. Number of Adverse Events Related to Study Drug Experienced by Participants After Second Bone Marrow Transplant (BMT) [12 months after second BMT]

      Serious and non-serious adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Secondary Outcome Measures

    1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) [Date treatment consent signed to date off study, approximately 79 months and 11 days.]

      Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    4 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • ELIGIBILITY CRITERIA:

    INCLUSION CRITERIA: TRANSPLANT RECIPIENT

    1. 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.

    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 (ALL)

    Adult: (greater than or equal to 22 years) greater than or equal to compete remission 2 (CR2) OR complete remission 1 (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 chronic myeloid leukemia (CML) are also eligible

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

    • High white blood cell (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 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 (< 44 chromosomes or deoxyribonucleic acid (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 karyotype (>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 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 (< 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 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

    1. 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.

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

    2. 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.

    1. Renal function: Patients must have evidence of adequate renal function to proceed with stem cell transplant, creatinine clearance > 60 ml/min/1.73 m(2). Glomerular filtration rate (GFR) may also demonstrate adequate renal function.

    2. 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).

    3. Pulmonary function of Diffusing Capacity of the Lung for Carbon Monoxide (DLC0) adj/alveolar volume (VA) and forced expiratory volume 1 (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 pulmonary function tests (PFTs) may be enrolled as per enrolling institution Standard Operating Procedure (SOP) for recipient guidelines.

    4. 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 this study.

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

    EXCLUSION CRITERIA: TRANSPLANT RECIPIENT

    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 principal investigator (PI) or associate investigator (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. Human immunodeficiency virus (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 Leuprolide intolerance. Note: patients ARE eligible if prior or current leuprolide exposure.

    INCLUSION CRITERIA: MATCHED RELATED TRANSPLANT DONOR

    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 Licensed Social Worker (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. Human leukocyte antigen (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 National Institutes of Health (NIH)/Clinical Center (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, human T-cell leukemia-lymphoma virus (HTLV) negative, hepatitis B surface antigen (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.

    EXCLUSION CRITERIA: MATCHED RELATED TRANSPLANT DONOR

    1. History of medical illness that in the estimation of the PI or Department of Transfusion Medicine (DTM) physician precludes donation of marrow.

    2. Anemia (Hemoglobin (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 cytomegalovirus (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.

    INCLUSION CRITERIA- MATCHED UNRELATED DONOR

    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.

    INCLUSION CRITERIA- (18F) FLT CANDIDATE TRANSPLANT RECIPIENT

    1. Meets criteria for Transplant Recipient

    2. Age greater than or equal to 18 years old at National Cancer Institute (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.

    EXCLUSION CRITERIA- (18F) FLT CANDIDATE TRANSPLANT RECIPIENT

    1. History of prior fluorothymidine allergy or intolerance.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Childrens National Medical Center Washington District of Columbia United States 20010
    2 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892
    3 University of Oklahoma Oklahoma City Oklahoma United States 73104

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Christopher G Kanakry, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Christopher Kanakry, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01338987
    Other Study ID Numbers:
    • 110136
    • 11-C-0136
    First Posted:
    Apr 20, 2011
    Last Update Posted:
    Mar 18, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Christopher Kanakry, M.D., Principal Investigator, National Cancer Institute (NCI)
    FLT
    Leuprolide
    Thymic Renewal
    Stem Cell Transplant
    Acute Lymphocytic Leukemia
    Acute Myelogenous Leukemia
    Myelodysplastic Syndrome
    Additional relevant MeSH terms:
    Leukemia
    Preleukemia
    Leukemia, Lymphoid
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Leukemia, Myeloid, Acute
    Leukemia, Myelomonocytic, Chronic
    Leukemia, Myelomonocytic, Juvenile
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Myelodysplastic Syndromes
    Alovudine
    Cyclophosphamide
    Busulfan
    Methotrexate
    Fludarabine
    Leuprolide
    Tacrolimus

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Arm/Group Description Males undergoing first transplant who did not receive leuprolide. Males undergoing first transplant who were randomized to receive leuprolide. Females undergoing first transplant who all received leuprolide. Individuals related to patients and who gave hematopoietic stem cells for patients receiving allogeneic bone marrow transplant on this study. Patients receiving second allogeneic bone marrow transplant on this study.
    Period Title: Overall Study
    STARTED 12 9 22 31 2
    COMPLETED 10 8 20 31 2
    NOT COMPLETED 2 1 2 0 0

    Baseline Characteristics

    Arm/Group Title Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant Total
    Arm/Group Description Males undergoing first transplant who did not receive leuprolide. Males undergoing first transplant who were randomized to receive leuprolide. Females undergoing first transplant who all received leuprolide. Individuals related to patients and who gave hematopoietic stem cells for patients receiving allogeneic bone marrow transplant on this study. Patients receiving second allogeneic Bone Marrow Transplant on this study. Total of all reporting groups
    Overall Participants 12 9 22 31 2 76
    Age (Count of Participants)
    <=18 years
    1
    8.3%
    0
    0%
    0
    0%
    3
    9.7%
    0
    0%
    4
    5.3%
    Between 18 and 65 years
    11
    91.7%
    9
    100%
    22
    100%
    28
    90.3%
    2
    100%
    72
    94.7%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    33
    (9.30)
    26.77
    (5.71)
    36.05
    (6.10)
    33.86
    (11.49)
    23.05
    (3.61)
    33.61
    (10.03)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    22
    100%
    17
    54.8%
    0
    0%
    39
    51.3%
    Male
    12
    100%
    9
    100%
    0
    0%
    14
    45.2%
    2
    100%
    37
    48.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    8
    66.7%
    6
    66.7%
    15
    68.2%
    26
    83.9%
    1
    50%
    56
    73.7%
    Not Hispanic or Latino
    4
    33.3%
    3
    33.3%
    7
    31.8%
    5
    16.1%
    1
    50%
    20
    26.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    4.5%
    1
    3.2%
    0
    0%
    2
    2.6%
    Asian
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    16.7%
    1
    11.1%
    3
    13.6%
    2
    6.5%
    0
    0%
    8
    10.5%
    White
    9
    75%
    5
    55.6%
    15
    68.2%
    28
    90.3%
    2
    100%
    59
    77.6%
    More than one race
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    1
    1.3%
    Unknown or Not Reported
    0
    0%
    2
    22.2%
    3
    13.6%
    0
    0%
    0
    0%
    5
    6.6%
    Region of Enrollment (Count of Participants)
    United States
    12
    100%
    9
    100%
    22
    100%
    31
    100%
    2
    100%
    76
    100%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of B Cells at One Year Post-transplant in Participants Who Did/Did Not Receive Leuprolide Following Bone Marrow Transplant (BMT)
    Description B cell percentage is defined as the percentage of lymphocytes that are B cells.
    Time Frame after first Bone Marrow Transplant, approximately 12 months post-transplant

    Outcome Measure Data

    Analysis Population Description
    Only first BMT patients (SG1-3) with >1 year of follow-up without relapse were evaluable. Of evaluable patients, 5 males and 9 females received and 7 males did not receive Lupron. Reasons for patients being inevaluable were missing data (2) or insufficient follow-up due to death without relapse (3), relapse (11), or withdrawal (1) before 1 year.
    Arm/Group Title Transplant Recipient
    Arm/Group Description Patients receiving first allogeneic bone marrow transplant on this study.
    Measure Participants 21
    Males that received leuprolide
    22.1
    Males that did not receive leuprolide
    21.9
    Females who all received leuprolide
    14.3
    2. Primary Outcome
    Title 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
    Description 18F-FLT imaging was performed serially on patients post transplant to identify the level of uptake of 18F-FLT at a day +5 to +12 scan and the day at which neutrophils recover to >500 (i.e., subclinical bone-marrow recovery within 5 days of Bone Marrow Transplantation (BMT infusion)). On each image for each patient, the region of interest was drawn within each thoracic medullary space (n=12), generating the SUV for each space. The mean of these was calculated for each scan. The analysis was the median of the means of the SUV of the thorax values of the day 5-12 scan (averaged the SUV of the thorax for each patient and then took the medians of these).
    Time Frame 18F FLT scan done between days +5 to +12 and then time from that scan to engraftment measured

    Outcome Measure Data

    Analysis Population Description
    The pre-specified cohort for this endpoint was 23 first BMT recipients. Only 20 of 23 were evaluable due to inability to obtain the early scan (1) or early relapse (2). As pre-specified in the protocol, all 20 patients were analyzed together as the intention was to look at the imaging modality itself and not any effect of leuprolide.
    Arm/Group Title Transplant Recipient
    Arm/Group Description Patients receiving first allogeneic bone marrow transplant on this study.
    Measure Participants 20
    Patients with SUV 1.4 or greater
    5
    Patients with SUV less than 1.4
    15
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Transplant Recipient
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0075
    Comments
    Method Wilcoxon's rank sum test
    Comments
    3. Primary Outcome
    Title Number of Adverse Events Related to Study Drug Experienced by Participants After Second Bone Marrow Transplant (BMT)
    Description Serious and non-serious adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame 12 months after second BMT

    Outcome Measure Data

    Analysis Population Description
    Only the patients in the SG4 group who had a 2nd BMT had a primary endpoint of toxicity requiring leuprolide AE reporting.
    Arm/Group Title Transplant Recipient - 2nd Bone Marrow Transplant
    Arm/Group Description Patients receiving second allogeneic bone marrow transplant on this study.
    Measure Participants 2
    Number [Adverse Events]
    0
    4. Secondary Outcome
    Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
    Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date treatment consent signed to date off study, approximately 79 months and 11 days.

    Outcome Measure Data

    Analysis Population Description
    40/45 transplant recipients and all 31 donors were evaluable for adverse events as five patients did not proceed to transplant after enrollment due to progression of disease in four cases and enrollment on a new protocol in one case.
    Arm/Group Title Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Arm/Group Description Males undergoing first transplant who did not receive leuprolide. Males undergoing first transplant who were randomized to receive leuprolide. Females undergoing first transplant who all received leuprolide. Individuals related to patients and who gave hematopoietic stem cells for patients receiving allogeneic Bone Marrow Transplant on this study. Patients receiving second allogeneic Bone Marrow Transplant on this study.
    Measure Participants 10 8 20 31 2
    Count of Participants [Participants]
    10
    83.3%
    8
    88.9%
    20
    90.9%
    4
    12.9%
    2
    100%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 79 months and 11 days.
    Adverse Event Reporting Description 40/45 participants were evaluable for adverse events.
    Arm/Group Title Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Arm/Group Description Males undergoing first transplant who did not receive leuprolide. Males undergoing first transplant who were randomized to receive leuprolide. Females undergoing first transplant who all received leuprolide. Individuals related to patients and who gave hematopoietic stem cells for patients receiving allogeneic bone marrow transplant on this study. Patients receiving second allogeneic bone marrow transplant on this study.
    All Cause Mortality
    Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/10 (40%) 3/8 (37.5%) 8/20 (40%) 0/31 (0%) 2/2 (100%)
    Serious Adverse Events
    Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/10 (50%) 6/8 (75%) 15/20 (75%) 2/31 (6.5%) 2/2 (100%)
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Febrile neutropenia 2/10 (20%) 3 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hemolysis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hemolytic uremic syndrome 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Cardiac disorders
    Pericardial effusion 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Sinus tachycardia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Eye disorders
    Cataract 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Corneal ulcer 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/10 (10%) 1 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Colitis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Colonic perforation 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Diarrhea 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Gastric hemorrhage 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Oral hemorrhage 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Typhlitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Upper gastrointestinal hemorrhage 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    General disorders
    Death NOS 1/10 (10%) 1 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Multi-organ failure 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Pain 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Hepatobiliary disorders
    Hepatic failure 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Immune system disorders
    Cytokine release syndrome 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations
    Catheter related infection 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, E.coli (blood, lungs) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Fever, neutropenia 1/10 (10%) 1 0/8 (0%) 0 5/20 (25%) 8 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Influenza H1N1 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Kaposi's sarcoma (HHV8) 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, PCP Pneumonia 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Parainfluenza III 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Presumed fungal 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Pseudomonas bacter 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, RSV 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Stenotrophom maltophilia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Stenotrophomonas bacteremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, adeno viremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed bacterial infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Candida glabrata in blood 0/10 (0%) 0 1/8 (12.5%) 2 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 2
    Lung infection 0/10 (0%) 0 2/8 (25%) 3 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Meningitis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Sepsis 0/10 (0%) 0 2/8 (25%) 2 4/20 (20%) 4 0/31 (0%) 0 0/2 (0%) 0
    Sinusitis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Upper respiratory infection 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Urinary tract infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and Infestations - Other, Candida glabrata in blood 0/10 (0%) 0 1/8 (12.5%) 2 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Blood bilirubin increased 0/10 (0%) 0 1/8 (12.5%) 2 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Metabolism and nutrition disorders
    Acidosis 1/10 (10%) 1 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Metabolism and nutrition disorders - Other, acidosis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Tumor lysis syndrome 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Musculoskeletal and connective tissue disorders
    Neck pain 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Nervous system disorders
    Syncope 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Psychiatric disorders
    Depression 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders
    Cystitis noninfective 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders - Other, renal failure 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Renal hemorrhage 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Aspiration 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Dyspnea 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Hypoxia 0/10 (0%) 0 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Pleural effusion 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Pneumonitis 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Pneumothorax 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Respiratory failure 1/10 (10%) 1 1/8 (12.5%) 2 4/20 (20%) 6 0/31 (0%) 0 2/2 (100%) 3
    Vascular disorders
    Hypotension 0/10 (0%) 0 0/8 (0%) 0 5/20 (25%) 8 2/31 (6.5%) 2 0/2 (0%) 0
    Other (Not Including Serious) Adverse Events
    Males That Did Not Receive Leuprolide for 1st Transplant Males Randomized to Receive Leuprolide for 1st Transplant Females That Received Leuprolide for 1st Transplant Matched Related Donors for Transplant Recipients of 2nd Transplant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/10 (100%) 8/8 (100%) 20/20 (100%) 4/31 (12.9%) 2/2 (100%)
    Blood and lymphatic system disorders
    Anemia 9/10 (90%) 28 5/8 (62.5%) 28 12/20 (60%) 39 3/31 (9.7%) 3 2/2 (100%) 4
    Febrile neutropenia 2/10 (20%) 2 2/8 (25%) 3 7/20 (35%) 7 0/31 (0%) 0 1/2 (50%) 2
    Cardiac disorders
    Atrial fibrillation 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Pericardial effusion 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Sinus bradycardia 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Sinus tachycardia 2/10 (20%) 2 1/8 (12.5%) 2 3/20 (15%) 3 0/31 (0%) 0 1/2 (50%) 2
    Ear and labyrinth disorders
    Hearing impaired 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Otitis externa 1/10 (10%) 1 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Endocrine disorders - Other, Hypoganadism 1/10 (10%) 1 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hypothyroidism 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Eye disorders
    Blurred vision 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Cataract 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Dry eye 1/10 (10%) 1 2/8 (25%) 2 4/20 (20%) 4 0/31 (0%) 0 0/2 (0%) 0
    Keratitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Retinal tear 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/10 (10%) 2 2/8 (25%) 3 6/20 (30%) 8 0/31 (0%) 0 1/2 (50%) 2
    Ascites 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 2
    Colitis 2/10 (20%) 2 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Colonic ulcer 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Constipation 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Diarrhea 4/10 (40%) 5 5/8 (62.5%) 6 10/20 (50%) 12 0/31 (0%) 0 2/2 (100%) 3
    Dry mouth 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Dyspepsia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Enterocolitis 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Esophagitis 1/10 (10%) 2 1/8 (12.5%) 2 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Gastritis 0/10 (0%) 0 1/8 (12.5%) 1 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Gastrointestinal disorders - Other, Melanotic Stool 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Gastroparesis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Ileal hemorrhage 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Mucositis oral 1/10 (10%) 1 3/8 (37.5%) 3 4/20 (20%) 4 0/31 (0%) 0 0/2 (0%) 0
    Nausea 4/10 (40%) 6 1/8 (12.5%) 2 9/20 (45%) 13 0/31 (0%) 0 1/2 (50%) 1
    Oral pain 3/10 (30%) 3 1/8 (12.5%) 3 4/20 (20%) 6 0/31 (0%) 0 1/2 (50%) 1
    Rectal mucositis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Small intestinal obstruction 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Typhlitis 0/10 (0%) 0 0/8 (0%) 0 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Upper gastrointestinal hemorrhage 0/10 (0%) 0 0/8 (0%) 0 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Vomiting 5/10 (50%) 5 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    General disorders
    Edema limbs 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Fatigue 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Fever 4/10 (40%) 5 2/8 (25%) 5 6/20 (30%) 7 0/31 (0%) 0 1/2 (50%) 1
    Hypothermia 0/10 (0%) 0 1/8 (12.5%) 2 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Pain 4/10 (40%) 5 2/8 (25%) 2 5/20 (25%) 5 0/31 (0%) 0 0/2 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/10 (10%) 1 0/8 (0%) 0 3/20 (15%) 4 0/31 (0%) 0 0/2 (0%) 0
    Hepatobiliary disorders - Other, Hepatic steatosis 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hepatobiliary disorders - Other, Ductal injury consistent w/GVHD, portal hypertension 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Hepatobiliary disorders - Other, acute liver injury 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Hepatobiliary disorders - Other, liver GVHD 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Immune system disorders
    Cytokine release syndrome 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations
    Catheter related infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Corneal infection 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, 6/24 Aeromonas infection of stool 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Adenoviremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Ascaris lubricoides in stool 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, BK cystitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, BK virus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Blood cultures were positive for GPC/bacteremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Blood cx: CMV+ ; CMV reactivation 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, C. diff 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, C. diff PCR+ 4/21 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, C. diff PCR+ 6/5 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV (blood) 2/10 (20%) 2 1/8 (12.5%) 1 2/20 (10%) 3 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV (blood, BAL, GI) 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV colitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 2 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV reactivation 2/10 (20%) 2 0/8 (0%) 0 6/20 (30%) 6 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV reactivation (1600 copies) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV reactivation (blood) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV reactivation +6350 copies 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV reactivation and presumed CMV infection of GI. 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV viremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV viremia, CMV gastritis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV-esophagitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Coagulase-negative Staph, Rhinovirus/enterovirus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Coronavirus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Coronavirus 229E (nasal wash, upper respiratory) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, E.coli (UTI) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, EBV+PCR 3600 copies 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, ESBL Klebsiella urinary tract infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, ESBL bacteremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Enteroaggregative E.coli (stool) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Enterococcus in blood 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Enteropathogenic E.coli (stool) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, GI tract 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Geotricum Capitatum 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Giardia 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, HHV6 (CSF) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, HSV oral ulcers 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Herpes zoster 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Human metapneumovirus 0/10 (0%) 0 0/8 (0%) 0 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Hypotension 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Influenza B 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Klebsiela pneumonia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Klebsiella, serratia, stenotrophomonas 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Lymphadenitis (inguinal lymph node) 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Mumps 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, NP wash - rhinovirus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Nocardia pulmonary infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, PICC, S.mitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Pleseimonas shigelloides (stool) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Presumed fungal - BAL (pulmonary) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Pseudomonas aeruginosa (skin lesion) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, RSV 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Rhino/enterovirus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Rhinovirus/enterovirus (NP wash) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Rotavirus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Rothia (Stomatococcus) mucilaginosus; 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, STAPH EPI from CSF 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Shiga-like E.coli (SREC) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Staph epi, Enterococcus faecalis in blood 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Staph. Capitis product infection 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, THRUSH 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, VRE bacteremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, VZV 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, VZV zoster 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Vancomycin-resistant Enterococcus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Varicella zoster (back, abdomen) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Varicella zoster- L thoracic area 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, adenovirus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, adenovirus viremia 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, bacterial vaginosis and C.albicans 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, bronchscopy - aspergillus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, clostridium tertium 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, coronaviral URI (intermittent) 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, fungal (yeast in blood) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, lung microbiology 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, norovirus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, oral candidiasis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, pneumonia-unknown organism 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed BK virus 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed bacterial 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed fungal pneumonia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 2 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed pneumonia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed pneumonia, yeast infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, presumed viral 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, rhinovirus/enterovirus 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, staph aureus (sinusitis) 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, Clostridium difficile - stool 2/10 (20%) 2 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Infections and infestations - Other, HHV-6 (alveolar inf.) 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Infections and infestations - Other, Human rhinovirus/enterovirus 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Infections and infestations - Other, Staph epidermitis in blood (port inf.) 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Infections and infestations - Other, intermittent bacteremia 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Lung infection 5/10 (50%) 7 3/8 (37.5%) 4 5/20 (25%) 7 0/31 (0%) 0 1/2 (50%) 1
    Meningitis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Sepsis 1/10 (10%) 1 2/8 (25%) 2 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Sinusitis 1/10 (10%) 1 1/8 (12.5%) 1 4/20 (20%) 4 0/31 (0%) 0 0/2 (0%) 0
    Soft tissue infection 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Urinary tract infection 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Vaginal infection 0/10 (0%) 0 0/8 (0%) 0 3/20 (15%) 5 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, pneumonia, presumed fungal 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, BK virus (urine infection) 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, CMV 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, staph aureus (sinusitis) 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Infections and infestations - Other, E. coli 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Injury, poisoning and procedural complications
    Fracture 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Injury, poisoning and procedural complications - Other, specify 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Stomal ulcer 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 2/10 (20%) 2 4/8 (50%) 4 6/20 (30%) 10 0/31 (0%) 0 1/2 (50%) 3
    Alanine aminotransferase increased 6/10 (60%) 24 4/8 (50%) 8 14/20 (70%) 45 0/31 (0%) 0 1/2 (50%) 3
    Alkaline phosphatase increased 3/10 (30%) 3 1/8 (12.5%) 6 5/20 (25%) 6 0/31 (0%) 0 1/2 (50%) 1
    Aspartate aminotransferase increased 5/10 (50%) 14 3/8 (37.5%) 5 13/20 (65%) 36 0/31 (0%) 0 0/2 (0%) 0
    Blood bilirubin increased 3/10 (30%) 4 2/8 (25%) 2 5/20 (25%) 10 0/31 (0%) 0 1/2 (50%) 2
    CPK increased 1/10 (10%) 2 2/8 (25%) 3 1/20 (5%) 2 0/31 (0%) 0 0/2 (0%) 0
    Carbon monoxide diffusing capacity decreased 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Creatinine increased 1/10 (10%) 2 2/8 (25%) 2 5/20 (25%) 7 0/31 (0%) 0 1/2 (50%) 1
    Ejection fraction decreased 1/10 (10%) 1 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Electrocardiogram QT corrected interval prolonged 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Fibrinogen decreased 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Lipase increased 1/10 (10%) 1 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Neutrophil count decreased 10/10 (100%) 49 7/8 (87.5%) 32 15/20 (75%) 83 0/31 (0%) 0 2/2 (100%) 2
    Platelet count decreased 10/10 (100%) 43 7/8 (87.5%) 53 14/20 (70%) 49 0/31 (0%) 0 2/2 (100%) 6
    Serum amylase increased 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Weight gain 0/10 (0%) 0 0/8 (0%) 0 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Weight loss 0/10 (0%) 0 1/8 (12.5%) 2 2/20 (10%) 5 0/31 (0%) 0 0/2 (0%) 0
    White blood cell decreased 10/10 (100%) 33 4/8 (50%) 46 16/20 (80%) 56 0/31 (0%) 0 2/2 (100%) 6
    Metabolism and nutrition disorders
    Acidosis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Alkalosis 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Anorexia 0/10 (0%) 0 0/8 (0%) 0 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Hypercalcemia 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hyperglycemia 3/10 (30%) 12 1/8 (12.5%) 1 5/20 (25%) 8 0/31 (0%) 0 0/2 (0%) 0
    Hyperkalemia 1/10 (10%) 1 2/8 (25%) 2 3/20 (15%) 4 0/31 (0%) 0 1/2 (50%) 1
    Hypermagnesemia 2/10 (20%) 4 1/8 (12.5%) 1 8/20 (40%) 9 0/31 (0%) 0 1/2 (50%) 1
    Hypernatremia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Hypertriglyceridemia 1/10 (10%) 2 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hyperuricemia 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Hypoalbuminemia 2/10 (20%) 3 1/8 (12.5%) 4 8/20 (40%) 9 0/31 (0%) 0 2/2 (100%) 2
    Hypocalcemia 1/10 (10%) 1 3/8 (37.5%) 3 4/20 (20%) 5 0/31 (0%) 0 1/2 (50%) 1
    Hypokalemia 6/10 (60%) 17 3/8 (37.5%) 5 10/20 (50%) 13 0/31 (0%) 0 1/2 (50%) 1
    Hypomagnesemia 2/10 (20%) 3 1/8 (12.5%) 1 4/20 (20%) 5 0/31 (0%) 0 1/2 (50%) 1
    Hyponatremia 2/10 (20%) 2 2/8 (25%) 2 3/20 (15%) 3 0/31 (0%) 0 2/2 (100%) 2
    Hypophosphatemia 8/10 (80%) 15 4/8 (50%) 6 12/20 (60%) 21 0/31 (0%) 0 2/2 (100%) 3
    Metabolism and nutrition disorders - Other, specify 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Musculoskeletal and connective tissue disorders
    Avascular necrosis 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Back pain 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Muscle weakness lower limb 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, Pain, bilateral shins/ankles R>L 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Myalgia 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Myositis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Neck pain 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Osteoporosis 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Pain in extremity 1/10 (10%) 1 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Nervous system disorders
    Cognitive disturbance 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Encephalopathy 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Headache 2/10 (20%) 2 1/8 (12.5%) 1 2/20 (10%) 2 0/31 (0%) 0 0/2 (0%) 0
    Peripheral sensory neuropathy 0/10 (0%) 0 0/8 (0%) 0 2/20 (10%) 2 1/31 (3.2%) 1 0/2 (0%) 0
    Psychiatric disorders
    Agitation 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Anxiety 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Confusion 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Delirium 1/10 (10%) 1 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Depression 2/10 (20%) 2 0/8 (0%) 0 2/20 (10%) 4 0/31 (0%) 0 1/2 (50%) 1
    Hallucinations 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Insomnia 2/10 (20%) 2 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Psychiatric disorders - Other, acute mental status changes 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Hematuria 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Proteinuria 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders - Other, renal insufficiency 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Urinary urgency 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Renal and urinary disorders - Other, membranous nephropathy 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Reproductive system and breast disorders
    Penile pain 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Reproductive system and breast disorders - Other, Dyspareunia, Vaginal dryness 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Reproductive system and breast disorders - Other, Vaginal bleeding 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Reproductive system and breast disorders - Other, vaginal scarring and stenosis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Aspiration 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Bronchopulmonary hemorrhage 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Cough 1/10 (10%) 2 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Dyspnea 1/10 (10%) 2 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 2
    Epistaxis 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Hypoxia 1/10 (10%) 2 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Pleural effusion 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Pneumonitis 1/10 (10%) 1 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Pneumothorax 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Upper respiratory infection 1/10 (10%) 3 1/8 (12.5%) 1 1/20 (5%) 2 0/31 (0%) 0 0/2 (0%) 0
    Skin and subcutaneous tissue disorders
    Dry skin 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Palmar-plantar erythrodysesthesia syndrome 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Papulopustular rash 1/10 (10%) 1 1/8 (12.5%) 1 3/20 (15%) 3 0/31 (0%) 0 0/2 (0%) 0
    Rash acneiform 3/10 (30%) 6 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Rash maculo-papular 3/10 (30%) 5 3/8 (37.5%) 3 5/20 (25%) 5 0/31 (0%) 0 1/2 (50%) 1
    Skin and subcutaneous tissue disorders - Other, Porokeratosis - buttocks 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Skin and subcutaneous tissue disorders - Other, cGVHD, scleroderma, rash 1/10 (10%) 1 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Skin and subcutaneous tissue disorders - Other, pimple-llike lesions neck, fase, chest 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Skin and subcutaneous tissue disorders - Other, rash 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Skin ulceration 2/10 (20%) 3 0/8 (0%) 0 0/20 (0%) 0 0/31 (0%) 0 0/2 (0%) 0
    Vascular disorders
    Capillary leak syndrome 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Hot flashes 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 2 0/31 (0%) 0 0/2 (0%) 0
    Hypertension 0/10 (0%) 0 1/8 (12.5%) 2 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Hypotension 0/10 (0%) 0 1/8 (12.5%) 1 1/20 (5%) 1 0/31 (0%) 0 1/2 (50%) 1
    Phlebitis 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0
    Thromboembolic event 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Vascular disorders - Other, Anasarca B/L 0/10 (0%) 0 1/8 (12.5%) 1 0/20 (0%) 0 0/31 (0%) 0 1/2 (50%) 1
    Vascular disorders - Other, TAM-transfusion associated microangiopathy 0/10 (0%) 0 0/8 (0%) 0 1/20 (5%) 1 0/31 (0%) 0 0/2 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Christopher Kanakry
    Organization National Cancer Institute
    Phone 240-760-6171
    Email christopher.kanakry@nih.gov
    Responsible Party:
    Christopher Kanakry, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01338987
    Other Study ID Numbers:
    • 110136
    • 11-C-0136
    First Posted:
    Apr 20, 2011
    Last Update Posted:
    Mar 18, 2021
    Last Verified:
    Mar 1, 2021