Trial Outcomes & Findings for Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients (NCT NCT02433483)

Last Updated: 2017-11-01

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

At the end of therapy cycle 2 (approximately 2-3 months)

Results posted on

2017-11-01

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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 Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route. Intrathecal Triples: given IT. HPC-A: Given IV.
Overall Study STARTED	2
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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 Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route. Intrathecal Triples: given IT. HPC-A: Given IV.
Overall Study Unacceptable toxicity	1
Overall Study Other antineoplastic therapy/HSCT	1

Baseline Characteristics

Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Myeloid Malignancies n=2 Participants 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.
Age, Continuous	7.45 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of therapy cycle 2 (approximately 2-3 months)

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Number of Participants by Stratum Who Complete 2 Cycles of Therapy	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Proportion of Participants Who Experience Therapeutic Success	0 proportion

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
3-year Event Free Survival (EFS)	0 Percentage of participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
3-year Overall Survival (OS)	0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Median Time to Neutrophil Recovery	14.5 Days Interval 12.0 to 17.0

SECONDARY outcome

Timeframe: From start of therapy to completion of therapy (approximately 1 year)

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

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.

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=1 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Time to Platelet Recovery	15 days

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Stage 0	0 Participants
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Stage I	0 Participants
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Stage II	0 Participants
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Stage III	2 Participants
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Stage IV	0 Participants

SECONDARY outcome

Timeframe: From start of therapy through completion of therapy (approximately 1 year)

Population: No patient survived long enough to evaluate chronic GVHD.

All grades of GVHD will be reported.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At weeks 1, 2, 3, and 4 after infusion of HPC-A

Percent donor chimerism in blood and bone marrow.

Outcome measures

Outcome measures
Measure	Myeloid Malignancies n=2 Participants Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.
Percent Donor Chimerism Week 1	79.5 Percentage of donor chimerism Interval 61.0 to 98.0
Percent Donor Chimerism Week 2	99 Percentage of donor chimerism Interval 98.5 to 99.5
Percent Donor Chimerism Week 3	99.5 Percentage of donor chimerism Interval 99.8 to 99.5
Percent Donor Chimerism Week 4	100 Percentage of donor chimerism Interval 100.0 to 100.0

Adverse Events

Myeloid Malignancies

Serious events: 1 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Myeloid Malignancies n=2 participants at risk 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.
Cardiac disorders Heart failure	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
General disorders Genderal disorders and administration site conditions	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Respiratory, thoracic and mediastinal disorders Pulmonary hypertention	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Respiratory, thoracic and mediastinal disorders Respiratory failure	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).

Other adverse events

Other adverse events
Measure	Myeloid Malignancies n=2 participants at risk 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.
Immune system disorders Graft Versus Host Disease	100.0% 2/2 • Number of events 2 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Blood and lymphatic system disorders Anemia	100.0% 2/2 • Number of events 13 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Blood and lymphatic system disorders Febrile Neutropenia	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Gastrointestinal disorders Abdominal pain	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
General disorders General disorders and administration site conditions	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Hepatobiliary disorders Gallbladder obstruction	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Infections and infestations Enterocolitis infectious	50.0% 1/2 • Number of events 2 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Infections and infestations Lung infection	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Infections and infestations Sepsis	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Infections and infestations Skin infection	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Infections and infestations Splenic infection	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Alanine aminotransferase increased	100.0% 2/2 • Number of events 4 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Aspartate aminotransferase increased	100.0% 2/2 • Number of events 5 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Blood bilirubin increased	100.0% 2/2 • Number of events 2 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations GGT increased	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Lymphocyte count decreased	100.0% 2/2 • Number of events 15 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Neutrophil count decreased	100.0% 2/2 • Number of events 4 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations Platelet count decreased	100.0% 2/2 • Number of events 22 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Investigations White blood cell decreased	100.0% 2/2 • Number of events 7 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Acidosis	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Alkalosis	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hypercalcemia	50.0% 1/2 • Number of events 6 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • Number of events 4 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hyperkalemia	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hypertriglyceridemia	100.0% 2/2 • Number of events 3 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hypocalcemia	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hypokalemia	100.0% 2/2 • Number of events 14 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Metabolism and nutrition disorders Hypophosphatemia	100.0% 2/2 • Number of events 5 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Respiratory, thoracic and mediastinal disorders Hypoxia	50.0% 1/2 • Number of events 2 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Respiratory, thoracic and mediastinal disorders Pleural effusion	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Vascular disorders Capillary leak syndrome	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).
Vascular disorders Hypotension	50.0% 1/2 • Number of events 1 • Adverse events were collected from date of participant start of therapy until off study date (up to 8 months).

Additional Information

Jeffrey E. Rubnitz, MD, PhD

St. Jude Children's Research Hospital

Phone: 901-595-2388

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place