Adoptive Transfer of Haplo-identical DLI for AML and MDS

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02046122
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary hypothesis is that chemotherapy followed by donor lymphocyte infusion (DLI) from HLA-haploidentical donors is a safe procedure that will not cause Graft versus Host Disease (GVHD) or increased treatment-related mortality. The Investigator further believes that this will improve outcomes of elderly patients with high-risk AML or MDS compared to chemotherapy alone, and that that this benefit will be even greater in donor-recipient pairs that share maternal-fetal microchimerism or non-inherited maternal antigen (NIMA) mismatch. A large part of this trial will include immune function assays as well as assessments of efficacy, toxicity, and GVHD. Because this therapy may be a tolerable alternative to allogeneic hematopoietic stem cell transplantation (alloHSCT) for elderly patients, the Investigator will validate functional measurements (e.g. Comprehensive Geriatric Assessment (CGA)) with biologic correlates (cytokine and genomic profiles) and clinical outcomes.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndrome	Drug: Idarubicin; Drug: Cytarabine; Biological: DLI	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Chemotherapy Combined With Adoptive Transfer of Human Leukocyte Antigen (HLA)-Haploidentical Donor Lymphocyte Infusion (DLI) in Older Patients With Righ-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Jun 15, 2017
• Actual Study Completion Date: Jul 31, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Idarubicin + Cytarabine + DLI Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)

Drug: Idarubicin; Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy.; Drug: Cytarabine; Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation.; Biological: DLI; HLA-mismatched DLI will be administered Day 9, approximately 24-48 hours following completion of chemotherapy at a dose of 1x10^8 cluster of differentiation 3 (CD3+) cells; however, due to logistics of planning infusions with staffing, donor availability, weekends/holidays, etc., it may be necessary to postpone cell infusion up to 96 hours. Given the time constraints presented by the need to start induction chemotherapy as soon as possible, in some cases, it may not be logistically possible to administer cells with induction. In these cases, patients would just receive standard induction chemotherapy and cells would be administered after consolidation 1 in addition to consolidation 2 Subjects who achieve a CR will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Unacceptable Toxicity [up to 8 weeks after last cell infusion]

   Unacceptable toxicity is defined as: i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days; ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days iii. Treatment-related mortality (TRM)

Secondary Outcome Measures

1. Disease Free Survival [one year following adoptive transfer]

   1 year disease free survival rate following adoptive transfer

2. Overall Survival [2 years after completing therapy]

   Number of participants alive 2 years after completing adoptive transfer therapy.

3. Percentage of Subjects With Acute GVHD [8 weeks after last cell infusion]

   Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days

4. Percentage of Subjects With Unacceptable Toxicity [8 weeks after the last cell infusion]

   Grade IV CTCAE toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days, Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days, or death

5. Rate of Efficacy [2 years after completing therapy]

   Efficacy as measured by the number of subjects with a complete remission. Responses were evaluated according to standard criteria defined by the National Comprehensive Cancer Network Guidelines for AML (www.nccn.org).

6. Number of Participants With Immune Recovery [up to 2 years after completing therapy]

   Immune recovery determined by measurements of cytokine profiles, lymphocyte and natural killer (NK) enumeration and flow-based assays, measured prior to induction, prior to each round of consolidation, 8 weeks after the last cycle of consolidation, and every 3 months after treatment for up to 2 years

7. Number of Days to Hematopoietic Recovery [2 years after completion of therapy]

   Hematopoietic recovery as measured by the date of the first of three consecutive laboratory values where the absolute neutrophil count (ANC) ≥ 500/μl , the date of the first of three consecutive laboratory values obtained on different days where the platelet count was > 20,000/μl without transfusion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects must have their diagnosis of high-risk AML or high-risk MDS confirmed by pathologic review of bone marrow biopsy according to WHO guidelines

2. Patients will be defined as high risk AML and thus eligible if they meet one or more of the following criteria:

3. Secondary AML (from underlying MDS or therapy related)

4. Presence of complex cytogenetic abnormalities (3 or more cytogenetic abnormalities), all monosomies, del 5q, del 7q, inv3, t(3;3), t(6;9), t(9;22), abn 11q23 (excluding t(9;11))

5. Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation positive

6. Age ≥ 65 years given poor outcomes even with favorable cytogenetics

7. Patients will be defined as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score ≥9

8. Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,or 2; if ECOG 2, they must also have a Charlson comorbidity index of ≤5.

9. Subjects must be 55 years of age or older

10. Subjects should have a 3-5/6 HLA-matched related haploidentical donor who is evaluated and deemed able to provide DLI.

11. Patient should be able to provide informed consent

12. Subjects must have a multigated acquisition (MUGA) and /or ECHO or cardiac magnetic resonance imaging (MRI). The required minimum standards include MUGA or ECHO or cardiac MR showing an ejection fraction( EF) of 40%. Those with an EF 40-49% must also have a cardiologist consult and assist with management.

13. Pulmonary function tests (PFTs) with diffusing capacity of lung for carbon monoxide (DLCO) are conditional for subjects at the discretion of the physician. The required minimum standards for those who have PFTs include DLCO of 40%. Those with DLCO of 40-49% must have a pulmonologist consult and assist with management.

14. Subjects of all genders and races are eligible

Exclusion Criteria:

1. Pregnant or lactating women.

2. Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol

3. Patients with known active central nervous system (CNS) disease

4. Patients with acute promyelocytic leukemia (FAB M3)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Anthony Sung, MD, Duke University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 10, 2017
• Informed Consent Form - Jan 4, 2018

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02046122
• Other Study ID Numbers: Pro00043247
• First Posted: Jan 27, 2014
• Last Update Posted: Dec 3, 2020
• Last Verified: Dec 1, 2020

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Cytarabine; Idarubicin

Study Results

Participant Flow

Pre-assignment Detail	1 subject was a screen failure and 1 subject withdrew prior to starting study.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Period Title: Overall Study
STARTED	17
COMPLETED	8
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71 (5)
Sex: Female, Male (Count of Participants)
Female	7 36.8%
Male	12 63.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	19 100%
Unknown or Not Reported	0 0%
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	3 15.8%
White	15 78.9%
More than one race	1 5.3%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Unacceptable Toxicity
Description	Unacceptable toxicity is defined as: i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days; ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days iii. Treatment-related mortality (TRM)
Time Frame	up to 8 weeks after last cell infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	17
Count of Participants [Participants]	1 5.3%

2. Secondary Outcome

Title	Disease Free Survival
Description	1 year disease free survival rate following adoptive transfer
Time Frame	one year following adoptive transfer

Outcome Measure Data

Analysis Population Description

Data not collected on one subject.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	16
Count of Participants [Participants]	3 15.8%

3. Secondary Outcome

Title	Overall Survival
Description	Number of participants alive 2 years after completing adoptive transfer therapy.
Time Frame	2 years after completing therapy

Outcome Measure Data

Analysis Population Description

Seventeen patients were enrolled between 2014 and 2017 with a median follow-up time of 299 days among all patients. One enrolled patient who developed sepsis during induction chemotherapy did not receive MST, and was excluded from final analysis of safety and efficacy.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	16
Number [participants]	16 84.2%

4. Secondary Outcome

Title	Percentage of Subjects With Acute GVHD
Description	Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days
Time Frame	8 weeks after last cell infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	17
Number [percentage of participants]	0 0%

5. Secondary Outcome

Title	Percentage of Subjects With Unacceptable Toxicity
Description	Grade IV CTCAE toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days, Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days, or death
Time Frame	8 weeks after the last cell infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	17
Number [percentage of participants]	5.88 30.9%

6. Secondary Outcome

Title	Rate of Efficacy
Description	Efficacy as measured by the number of subjects with a complete remission. Responses were evaluated according to standard criteria defined by the National Comprehensive Cancer Network Guidelines for AML (www.nccn.org).
Time Frame	2 years after completing therapy

Outcome Measure Data

Analysis Population Description

Data not collected on one subject.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	16
Count of Participants [Participants]	10 52.6%

7. Secondary Outcome

Title	Number of Participants With Immune Recovery
Description	Immune recovery determined by measurements of cytokine profiles, lymphocyte and natural killer (NK) enumeration and flow-based assays, measured prior to induction, prior to each round of consolidation, 8 weeks after the last cycle of consolidation, and every 3 months after treatment for up to 2 years
Time Frame	up to 2 years after completing therapy

Outcome Measure Data

Analysis Population Description

Data not collected on one subject.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	16
Count of Participants [Participants]	3 15.8%

8. Secondary Outcome

Title	Number of Days to Hematopoietic Recovery
Description	Hematopoietic recovery as measured by the date of the first of three consecutive laboratory values where the absolute neutrophil count (ANC) ≥ 500/μl , the date of the first of three consecutive laboratory values obtained on different days where the platelet count was > 20,000/μl without transfusion.
Time Frame	2 years after completion of therapy

Outcome Measure Data

Analysis Population Description

Data not collected on one subject.

Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
Measure Participants	16
Neutrophil recovery	29
Platelet recovery	32

Adverse Events

Time Frame	All serious adverse events (SAEs) that occur up to 30 days after the last Donor Lymphocyte Infusion (DLI) will be reported.
Adverse Event Reporting Description	After 30 days, SAEs will be reported if thought related to treatment for the duration of the study. Non-treatment related SAEs were not collected past 30 days after the last DLI.
Arm/Group Title	Idarubicin + Cytarabine + DLI
Arm/Group Description	Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI) Idarubicin: Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine: Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after
All Cause Mortality
	Idarubicin + Cytarabine + DLI
	Affected / at Risk (%)	# Events
Total	12/17 (70.6%)
Serious Adverse Events
	Idarubicin + Cytarabine + DLI
	Affected / at Risk (%)	# Events
Total	8/17 (47.1%)
Blood and lymphatic system disorders
Febrile neutropenia	1/17 (5.9%)	1
Cardiac disorders
Atrial fibrillation	1/17 (5.9%)	1
Gastrointestinal disorders
Ileus	1/17 (5.9%)	1
Mucositis oral	1/17 (5.9%)	1
General disorders
Multi-organ failure	1/17 (5.9%)	1
Hepatobiliary disorders
Hepatic failure	1/17 (5.9%)	1
Infections and infestations
Urinary tract infection	1/17 (5.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	1/17 (5.9%)	1
Psychiatric disorders
Delirium	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Idarubicin + Cytarabine + DLI
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	13/17 (76.5%)	65
Blood and lymphatic system disorders other	4/17 (23.5%)	7
Febrile neutropenia	13/17 (76.5%)	21
Cardiac disorders
Atrial fibrillation	1/17 (5.9%)	1
cardiac disorders other	1/17 (5.9%)	1
Ear and labyrinth disorders
Hearing impaired	1/17 (5.9%)	1
Eye disorders
eye disorders other	1/17 (5.9%)	1
Gastrointestinal disorders
Abdominal pain	1/17 (5.9%)	1
Mucositis oral	1/17 (5.9%)	1
General disorders
Fatigue	3/17 (17.6%)	3
Infections and infestations
Fever	1/17 (5.9%)	1
general disorders and administration site conditions	1/17 (5.9%)	1
Infections and infestations other	2/17 (11.8%)	2
Lung infection	1/17 (5.9%)	1
Penile infection	1/17 (5.9%)	1
Sepsis	6/17 (35.3%)	6
Splenic infection	1/17 (5.9%)	1
Urinary tract infection	3/17 (17.6%)	3
Investigations
Blood bilirubin increased	2/17 (11.8%)	2
Creatinine increased	1/17 (5.9%)	1
ECG QT corrected interval prolonged	1/17 (5.9%)	1
Lymphocyte count decreased	1/17 (5.9%)	2
Neutrophil count decreased	11/17 (64.7%)	16
Platelet count decreased	17/17 (100%)	34
White blood cell decreased	16/17 (94.1%)	28
Metabolism and nutrition disorders
Acidosis	1/17 (5.9%)	2
Alkalosis	1/17 (5.9%)	3
Anorexia	1/17 (5.9%)	1
Hyperglycemia	7/17 (41.2%)	18
Hyperkalemia	1/17 (5.9%)	1
Hypoalbuminemia	7/17 (41.2%)	8
Hypocalcemia	1/17 (5.9%)	1
Hypokalemia	11/17 (64.7%)	26
Hyponatremia	2/17 (11.8%)	4
Hypophosphatemia	2/17 (11.8%)	2
Tumor lysis syndrome	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/17 (5.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
treatment related secondary malignancy	1/17 (5.9%)	1
Nervous system disorders
peripheral sensory neuropathy	1/17 (5.9%)	1
Syncope	1/17 (5.9%)	1
Renal and urinary disorders
Acute kidney injury	1/17 (5.9%)	1
Hematuria	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/17 (11.8%)	3
Pneumonitis	1/17 (5.9%)	1
Pulmonary edema	2/17 (11.8%)	2
Respiratory failure	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders other	2/17 (11.8%)	2
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/17 (5.9%)	1
Vascular disorders
Hypertension	3/17 (17.6%)	4
Hypotension	3/17 (17.6%)	4

Limitations/Caveats

[Not Specified]

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.