Trial Outcomes & Findings for Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies (NCT NCT01028716)

NCT ID: NCT01028716

Last Updated: 2023-01-23

Results Overview

Cumulative incidence of death without evidence of disease progression at 1 year

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Up to 1 year
• Results posted on: 2023-01-23

Participant Flow

Participant milestones

Measure	Treatment (Nonmyeloablative HCT, TBI) Conditioning: Fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Cell product: Patients undergo donor peripheral blood stem cell transplant on day 0. GVHD Prophylaxis: Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.
Overall Study STARTED	46
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Treatment (Nonmyeloablative HCT, TBI) Conditioning: Fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Cell product: Patients undergo donor peripheral blood stem cell transplant on day 0. GVHD Prophylaxis: Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Overall Study Physician Decision

1

Baseline Characteristics

Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Baseline characteristics by cohort

Measure	Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.
Age, Continuous	52 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	7 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	4 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Cumulative incidence of death without evidence of disease progression at 1 year

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Non-relapse Mortality at 1 Year

22 percent of participants

PRIMARY outcome

Timeframe: Up to 2 years post-transplant

Population: Patients who were alive greater than day 100 were included

Scored according to the National Cancer Institute criteria. Mild-to-severe chronic GVHD at 2 years.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=41 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Percentage of Participants With Chronic Graft Versus Host Disease

26 percentage of participants

PRIMARY outcome

Timeframe: At day 84

Grading determined by organ system stages. Grade III/IV acute graft versus host disease is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Incidence of Grades III/IV Acute Graft Versus Host Disease

82 percent

PRIMARY outcome

Timeframe: Up to 7 years

Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Relapse of Malignancy After Transplantation

29 percent

SECONDARY outcome

Timeframe: Up to day 84 post-transplant

Achievement of an absolute neutrophil count greater or equal to 500/mm^3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Time to Neutrophil Recovery

16 days Interval 13.0 to 29.0

SECONDARY outcome

Timeframe: Up to day 84 post-transplant

The first day of a sustained platelet count > 20,000/mm^3 with no platelet transfusions in the preceding seven days.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=42 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Time to Platelet Recovery

23 days Interval 17.0 to 50.0

SECONDARY outcome

Timeframe: At day 84

Defined as < 5% donor CD3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Incidence of Primary Graft Failure

0 Participants

SECONDARY outcome

Timeframe: 3 years from the date of transplant

Defined as being alive and in remission by < 5% blasts by bone marrow morphology for patients with myeloid malignancies and CT or PET imaging for patients with lymphoid malignancies at the time of the assessment

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Disease-free Survival

40 percent of participants

SECONDARY outcome

Timeframe: Up to day 90

Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 was determined.

Outcome measures

Measure	Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Cardiac	13 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Fever	9 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Rash	4 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Gastrointestinal	17 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Infections	55 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System CMV Reactivation	26 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Febrile Neutropenia	25 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Metabolic/laboratory	24 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Musculoskeletal	3 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Neurologic	5 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Pain	6 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Pulmonary	10 events
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System Renal/Genitourinary	10 events

SECONDARY outcome

Timeframe: Day 0-100

Number of units of RBCs given to the patient between day 0 and day 100 post transplant

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Number of Red Blood Cell Transfusions

8 transfusions Interval 0.0 to 32.0

SECONDARY outcome

Timeframe: Day 0-100

Number platelet transfusions given to the patient between day 0 and day 100 post transplant

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Number of Platelet Transfusions

6 transfusions Interval 1.0 to 52.0

SECONDARY outcome

Timeframe: 3 years

Kaplan Meier estimate of the percentage of participants with overall survival at 3 years

Outcome measures

Measure

Treatment (Nonmyeloablative HCT, TBI) n=45 Participants Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Point Estimate of Overall Survival at 3 Years

45.3 percent

Adverse Events

Treatment (Nonmyeloablative HCT, TBI)

Serious events: 4 serious events

Other events: 44 other events

Deaths: 21 deaths

Serious adverse events

Measure	Treatment (Nonmyeloablative HCT, TBI) n=45 participants at risk Conditioning: Fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Cell product: Patients undergo donor peripheral blood stem cell transplant on day 0. GVHD Prophylaxis: Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.
Respiratory, thoracic and mediastinal disorders ARDS	2.2% 1/45 • Number of events 2 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Cardiac disorders Heart Failure	2.2% 1/45 • Number of events 1 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Respiratory, thoracic and mediastinal disorders Diffuse Alveolar Hemorrhage	2.2% 1/45 • Number of events 1 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Respiratory, thoracic and mediastinal disorders Acute hypoxemia respiratory failure	2.2% 1/45 • Number of events 1 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.

Other adverse events

Measure	Treatment (Nonmyeloablative HCT, TBI) n=45 participants at risk Conditioning: Fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Cell product: Patients undergo donor peripheral blood stem cell transplant on day 0. GVHD Prophylaxis: Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.
Cardiac disorders Cardiac	28.9% 13/45 • Number of events 13 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Infections and infestations Infection	93.3% 42/45 • Number of events 115 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Musculoskeletal and connective tissue disorders Pain	13.3% 6/45 • Number of events 9 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Metabolism and nutrition disorders Metabolic	33.3% 15/45 • Number of events 24 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Respiratory, thoracic and mediastinal disorders Pulmonary	22.2% 10/45 • Number of events 10 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Gastrointestinal disorders GI	28.9% 13/45 • Number of events 17 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Renal and urinary disorders Renal	11.1% 5/45 • Number of events 10 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.
Skin and subcutaneous tissue disorders Derm	4.4% 2/45 • Number of events 4 • Adverse events were collected for up to 100 days post HCT. Serious Adverse Events were collected until 1 year post-HCT. All cause mortality was assessed up to 3 years post transplant.

Additional Information

Rachel Salit

Fred Hutchinson Cancer Center

Phone: 2066671317

Email: rsalit@fredhutch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place