Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02433483
• Collaborator: Cookies for Kids' Cancer (Other)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 23.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient.

Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease.

With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)	Drug: Cytarabine; Drug: Intrathecal Triples; Biological: HPC-A	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

• To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or refractory hematologic malignancies.

• To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in pediatric patients with relapsed or refractory hematologic malignancies.

SECONDARY OBJECTIVES:

• To describe the event-free and overall survival of patients treated with standard chemotherapy plus GCSF-mobilized HPC-A.

• To estimate the time to neutrophil and platelet recovery after treatment with standard chemotherapy plus GCSF-mobilized HPC-A.

• To determine the cumulative incidence of acute and chronic graft-versus-host disease (GVHD).

OTHER PRESPECIFIED OBJECTIVES:

• To characterize donor chimerism and microchimerism.

Patients will receive standard chemotherapy followed by infusion of donor peripheral blood mononuclear cells 2 days after the completion of chemotherapy. Patients who have at least a partial response are eligible to receive a second cycle.

Diagnostic lumbar puncture and intrathecal (IT) chemotherapy will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly IT therapy (age-adjusted methotrexate, hydrocortisone, and cytarabine) until the cerebrospinal fluid (CSF) becomes free of leukemia (minimum of 4 doses).

Bone marrow aspiration (BMA) and biopsy to assess response will be performed on approximately day 29 of therapy.

For hematopoietic stem cell mobilization, donors will receive G-CSF (Filgrastim) (Neupogen®) each day for 5 days given subcutaneously (SQ) prior to HPC-A collected by leukapheresis on day 6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Microtransplantation in Patients With Refractory or Relapsed Hematologic Malignancies
• Actual Study Start Date: May 22, 2015
• Actual Primary Completion Date: May 8, 2017
• Actual Study Completion Date: May 8, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Myeloid Malignancies Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: Cycle 1: cytarabine, HPC-A donor infusion Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion

Drug: Cytarabine; Given by either intrathecal (IT) or intravenous (IV) route.; Other Names: Cytosine arabinoside Ara-C Cytosar® ; Drug: Intrathecal Triples; given IT.; Other Names: ITMHA Methotrexate/hydrocortisone/cytarabine ; Biological: HPC-A; Given IV.; Other Names: Donor infusion Hematopoietic Progenitor Cell, Apheresis

Outcome Measures

Primary Outcome Measures

1. Number of Participants by Stratum Who Complete 2 Cycles of Therapy [At the end of therapy cycle 2 (approximately 2-3 months)]

   If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as >5% donor chimerism at the time of count recovery (ANC > 0.3 x 10^9/L and platelet count > 30 x 10^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.

2. Proportion of Participants Who Experience Therapeutic Success [At the end of therapy cycle 2 (approximately 2-3 months)]

   All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as: Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy. Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy. In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.

Secondary Outcome Measures

1. 3-year Event Free Survival (EFS) [3 years after enrollment of the last participant]

   We will use the Kaplan-Meier method to describe event-free survival. EFS will be defined as the time from enrollment to death, relapse, or refractory disease with event-free subjects' time censored at the date of last follow-up.

2. 3-year Overall Survival (OS) [3 years after enrollment of the last participant]

   We will use the Kaplan-Meier method to describe overall survival. Overall survival will be defined as the time from enrollment to death, with living subjects' time censored at the date of last follow-up

3. Median Time to Neutrophil Recovery [From start of therapy to completion of therapy (approximately 1 year)]

   The time to neutrophil recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of neutrophils, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.

4. Time to Platelet Recovery [From start of therapy to completion of therapy (approximately 1 year)]

   The time to platelet recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of platelets, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events. Due to the small number of patients enrolled, the data is presented by patient.

5. 1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) [From start of therapy through completion of therapy (approximately 1 year)]

   Children's Oncology Group (COG) Stem Cell Committee Consensus Guidelines for Establishing Organ Stage and Overall Grade of Acute Graft Versus Host Disease (GVHD) were used. Overall clinical grade was based on the highest stage obtained: Grade 0: no stage 1-4 of any organ Grade I: stage 1-2 skin and no liver or gut involvement Grade II: stage 3 skin, or stage 1 liver involvement, or stage 1 GI Grade III: stage 0-3 skin, with stage 2-3 liver, or stage 2-3 GI Grade IV: stage 4 skin, liver or GI involvement

6. 1-year Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD) [From start of therapy through completion of therapy (approximately 1 year)]

   All grades of GVHD will be reported.

Other Outcome Measures

1. Percent Donor Chimerism [At weeks 1, 2, 3, and 4 after infusion of HPC-A]

   Percent donor chimerism in blood and bone marrow.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA - AML and MDS PARTICIPANTS

• Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after HSCT.

• Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.

• Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have converted from negative minimal residual disease (MRD) status to positive MRD status in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.

• Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).

• Adequate organ function defined as the following:

• Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.5 mg/dL

• AST (SGOT)/ALT (SGPT) < 5 x ULN

• Calculated creatinine clearance > 50 ml/min/1.73m^2 as calculated by the Schwartz formula for estimated glomerular filtration rate >

• Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.

• Has an available HPC-A donor.

• Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.

• Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.

• Patient has fully recovered from the acute effects of all prior therapy and must meet the following criteria.

• At least 14 days must have elapsed since the completion of myelosuppressive therapy.

• At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose cytarabine (up to 200 mg/m^2/day), and intrathecal chemotherapy.

• At least 30 days must have elapsed since the use of investigational agents.

• For patients who have received prior HSCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HSCT. Patients cannot be receiving therapy, including steroids, for GVHD.

• Post-menarchal female has had negative serum pregnancy test within 7 days prior to enrollment.

• Male or female of reproductive potential has agreed to use effective contraception for the duration of study participation.

• Not breastfeeding

INCLUSION CRITERIA - HPC-A CELL DONOR

• At least 18 years of age.

• Family member (first degree relatives).

• Not pregnant as confirmed by negative serum or urine pregnancy test within 7 days prior to enrollment (if female).

• Not breast feeding.

• Meets donation eligibility requirements as outlined by 21 CFR 1271.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• Cookies for Kids' Cancer

Investigators

• Principal Investigator: Jeffrey E. Rubnitz, MD, PhD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan: Initial Protocol - Apr 14, 2015
• Study Protocol and Statistical Analysis Plan: Version 1.0 - Dec 1, 2015

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT02433483
• Other Study ID Numbers: MITREL; NCI-2015-00691
• First Posted: May 5, 2015
• Last Update Posted: Nov 1, 2017
• Last Verified: Sep 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by St. Jude Children's Research Hospital: Adolescent; Children; Microtransplant; Leukemia
• Additional relevant MeSH terms: Leukemia, Myeloid, Acute; Preleukemia; Hematologic Neoplasms; Myelodysplastic Syndromes; Cytarabine; Hydrocortisone; Methotrexate

Study Results

Participant Flow

Recruitment Details	Two participants and 2 bone marrow or blood stem cell donors were enrolled at St. Jude Children's Research Hospital between May 2015 and July 2015. The donors do not undergo protocol therapy interventions and are not included in the results reporting provided here.

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: Cycle 1: cytarabine, HPC-A donor infusion Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route. Intrathecal Triples: given IT. HPC-A: Given IV.
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: Cycle 1: cytarabine, HPC-A donor infusion Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route. Intrathecal Triples: given IT. HPC-A: Given IV.
Overall Participants	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	7.45
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants by Stratum Who Complete 2 Cycles of Therapy
Description	If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as >5% donor chimerism at the time of count recovery (ANC > 0.3 x 10^9/L and platelet count > 30 x 10^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.
Time Frame	At the end of therapy cycle 2 (approximately 2-3 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Proportion of Participants Who Experience Therapeutic Success
Description	All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as: Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy. Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy. In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.
Time Frame	At the end of therapy cycle 2 (approximately 2-3 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Number [proportion]	0

3. Secondary Outcome

Title	3-year Event Free Survival (EFS)
Description	We will use the Kaplan-Meier method to describe event-free survival. EFS will be defined as the time from enrollment to death, relapse, or refractory disease with event-free subjects' time censored at the date of last follow-up.
Time Frame	3 years after enrollment of the last participant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Number [Percentage of participants]	0 0%

4. Secondary Outcome

Title	3-year Overall Survival (OS)
Description	We will use the Kaplan-Meier method to describe overall survival. Overall survival will be defined as the time from enrollment to death, with living subjects' time censored at the date of last follow-up
Time Frame	3 years after enrollment of the last participant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Number [Percentage of participants]	0 0%

5. Secondary Outcome

Title	Median Time to Neutrophil Recovery
Description	The time to neutrophil recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of neutrophils, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.
Time Frame	From start of therapy to completion of therapy (approximately 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Median (Full Range) [Days]	14.5

6. Secondary Outcome

Title	Time to Platelet Recovery
Description	The time to platelet recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of platelets, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events. Due to the small number of patients enrolled, the data is presented by patient.
Time Frame	From start of therapy to completion of therapy (approximately 1 year)

Outcome Measure Data

Analysis Population Description

Platelet recovery for Patient #1 could not be determined due to transfusions.

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	1
Number [days]	15

7. Secondary Outcome

Title	1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)
Description	Children's Oncology Group (COG) Stem Cell Committee Consensus Guidelines for Establishing Organ Stage and Overall Grade of Acute Graft Versus Host Disease (GVHD) were used. Overall clinical grade was based on the highest stage obtained: Grade 0: no stage 1-4 of any organ Grade I: stage 1-2 skin and no liver or gut involvement Grade II: stage 3 skin, or stage 1 liver involvement, or stage 1 GI Grade III: stage 0-3 skin, with stage 2-3 liver, or stage 2-3 GI Grade IV: stage 4 skin, liver or GI involvement
Time Frame	From start of therapy through completion of therapy (approximately 1 year)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Stage 0	0 0%
Stage I	0 0%
Stage II	0 0%
Stage III	2 100%
Stage IV	0 0%

8. Other Pre-specified Outcome

Title	Percent Donor Chimerism
Description	Percent donor chimerism in blood and bone marrow.
Time Frame	At weeks 1, 2, 3, and 4 after infusion of HPC-A

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	2
Week 1	79.5
Week 2	99
Week 3	99.5
Week 4	100

9. Secondary Outcome

Title	1-year Cumulative Incidence of Chronic Graft Versus Host Disease (GVHD)
Description	All grades of GVHD will be reported.
Time Frame	From start of therapy through completion of therapy (approximately 1 year)

Outcome Measure Data

Analysis Population Description

No patient survived long enough to evaluate chronic GVHD.

Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Arm/Group Title	Myeloid Malignancies
Arm/Group Description	Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: Cycle 1: cytarabine, HPC-A donor infusion Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route. Intrathecal Triples: given IT. HPC-A: Given IV.
All Cause Mortality
	Myeloid Malignancies
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Serious Adverse Events
	Myeloid Malignancies
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Cardiac disorders
Heart failure	1/2 (50%)	1
General disorders
Genderal disorders and administration site conditions	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertention	1/2 (50%)	1
Respiratory failure	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Myeloid Malignancies
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Anemia	2/2 (100%)	13
Febrile Neutropenia	2/2 (100%)	3
Gastrointestinal disorders
Abdominal pain	1/2 (50%)	1
General disorders
General disorders and administration site conditions	1/2 (50%)	1
Hepatobiliary disorders
Gallbladder obstruction	1/2 (50%)	1
Immune system disorders
Graft Versus Host Disease	2/2 (100%)	2
Infections and infestations
Enterocolitis infectious	1/2 (50%)	2
Lung infection	2/2 (100%)	3
Sepsis	1/2 (50%)	1
Skin infection	1/2 (50%)	1
Splenic infection	1/2 (50%)	1
Investigations
Alanine aminotransferase increased	2/2 (100%)	4
Aspartate aminotransferase increased	2/2 (100%)	5
Blood bilirubin increased	2/2 (100%)	2
GGT increased	2/2 (100%)	3
Lymphocyte count decreased	2/2 (100%)	15
Neutrophil count decreased	2/2 (100%)	4
Platelet count decreased	2/2 (100%)	22
White blood cell decreased	2/2 (100%)	7
Metabolism and nutrition disorders
Acidosis	2/2 (100%)	3
Alkalosis	2/2 (100%)	3
Hypercalcemia	1/2 (50%)	6
Hyperglycemia	1/2 (50%)	4
Hyperkalemia	1/2 (50%)	1
Hypertriglyceridemia	2/2 (100%)	3
Hypocalcemia	1/2 (50%)	1
Hypokalemia	2/2 (100%)	14
Hypophosphatemia	2/2 (100%)	5
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/2 (50%)	1
Hypoxia	1/2 (50%)	2
Pleural effusion	1/2 (50%)	1
Vascular disorders
Capillary leak syndrome	1/2 (50%)	1
Hypotension	1/2 (50%)	1

Limitations/Caveats

This study was terminated in May 2017 due to poor accrual and because of competing protocols.

More Information

Certain Agreements

All Principal Investigators ARE 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.