Trial Outcomes & Findings for Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (NCT NCT03023046)

Last Updated: 2022-07-13

Results Overview

Morphological complete remission (CR) was determined by bone marrow aspirate morphology and defined as \<5% blasts by morphology, absolute neutrophil count \>1000/uL, and platelet count \>100,000/uL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Within 4 cycles of study therapy

Results posted on

2022-07-13

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Chemotherapy) Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Dasatinib: Given PO Doxorubicin: Given IV Etoposide: Given IV Imatinib Mesylate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Overall Study STARTED	54
Overall Study COMPLETED	53
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Chemotherapy) Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Dasatinib: Given PO Doxorubicin: Given IV Etoposide: Given IV Imatinib Mesylate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Chemotherapy) n=53 Participants Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Dasatinib: Given PO Doxorubicin: Given IV Etoposide: Given IV Imatinib Mesylate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Age, Continuous	49 years n=99 Participants
Sex: Female, Male Female	28 Participants n=99 Participants
Sex: Female, Male Male	25 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants
Race (NIH/OMB) White	46 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
High white blood cell count	11 Participants n=99 Participants
Lineage B-cell	49 Participants n=99 Participants
Lineage T-cell	4 Participants n=99 Participants
Philadelphia chromosome Philadelphia chromosome: positive	28 Participants n=99 Participants
Philadelphia chromosome Philadelphia chromosome: negative	25 Participants n=99 Participants

PRIMARY outcome

Timeframe: Within 4 cycles of study therapy

Morphological complete remission (CR) was determined by bone marrow aspirate morphology and defined as \<5% blasts by morphology, absolute neutrophil count \>1000/uL, and platelet count \>100,000/uL.

Outcome measures

Outcome measures
Measure	Ph+ Subjects n=28 Participants Subjects who have Philadelphia chromosome mutation	Ph- Subjects n=25 Participants Subjects who do not have Philadelphia chromosome mutation
Number of Participants With Morphological Complete Response Rate	27 Participants	20 Participants

PRIMARY outcome

Timeframe: Within 4 cycles of study therapy

Population: HTS- percentages were calculated after excluding patients (Ph+, n = 4; Ph-, n = 3) that were unable to have HTS testing performed for technical reasons.

Response was determined by having no detectable disease by multiparameter flow cytometry (MFC-). For Ph+ subjects, complete molecular response (CMR) by BCR-ABL RT-PCR was assigned when MFC was undetectable. When no measurable residual disease was detected by MFC (MFC-) per EuroFlow criteria, high-throughput sequencing-based MRD testing (HTS; ClonoSEQ) was performed.

Outcome measures

Outcome measures
Measure	Ph+ Subjects n=28 Participants Subjects who have Philadelphia chromosome mutation	Ph- Subjects n=25 Participants Subjects who do not have Philadelphia chromosome mutation
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate MFC- · Achieve within 4 cycles	20 Participants	16 Participants
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate MFC- · Not achieved within 4 cycles	8 Participants	9 Participants
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate CMR · Achieve within 4 cycles	11 Participants	—
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate CMR · Not achieved within 4 cycles	17 Participants	—
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate HTS- · Achieve within 4 cycles	8 Participants	6 Participants
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate HTS- · Not achieved within 4 cycles	16 Participants	16 Participants

SECONDARY outcome

Timeframe: Within 28 days of the last dose of the study drugs

Grade 1 or higher non-hematologic adverse events will be assessed by Common Terminology Criteria for Adverse Events version 5.0.

Outcome measures

Outcome measures
Measure	Ph+ Subjects n=53 Participants Subjects who have Philadelphia chromosome mutation	Ph- Subjects Subjects who do not have Philadelphia chromosome mutation
Number of Participants With Adverse Events	44 Participants	—

SECONDARY outcome

Timeframe: Up to 2 years

Alive at 2 years after enrollment

Outcome measures

Outcome measures
Measure	Ph+ Subjects n=53 Participants Subjects who have Philadelphia chromosome mutation	Ph- Subjects Subjects who do not have Philadelphia chromosome mutation
Overall Survival	70 Percentage of Participants	—

SECONDARY outcome

Timeframe: Up to 2 years

Events were defined as any of the following: (1) unable to achieve either morphologic complete remission (CR) or MRD- by MFC, (2) relapse after CR, (3) MRD recurrence after achieving MRD-, or (4) death from any cause.

Outcome measures

Outcome measures
Measure	Ph+ Subjects n=53 Participants Subjects who have Philadelphia chromosome mutation	Ph- Subjects Subjects who do not have Philadelphia chromosome mutation
Event-free Survival	32 Percentage of Participants	—

Adverse Events

Treatment (Chemotherapy)

Serious events: 32 serious events

Other events: 14 other events

Deaths: 18 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Chemotherapy) n=53 participants at risk Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Dasatinib: Given PO Doxorubicin: Given IV Etoposide: Given IV Imatinib Mesylate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Respiratory, thoracic and mediastinal disorders Aspiration	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Cardiac disorders Atrial fibrillation	1.9% 1/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Psychiatric disorders Delirium	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Infections and infestations Endophthalmitis	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Enterocolitis	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Blood and lymphatic system disorders Febrile neutropenia	26.4% 14/53 • Number of events 19 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Investigations Fibrinogen decreased	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Infections and infestations Fungemia	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Vascular disorders Hypotension	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Nervous system disorders Intracranial hemorrhage	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Infections and infestations Kidney infection	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Mucositis oral	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Cardiac disorders Myocardial infarction	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Nervous system disorders Peripheral motor neuropathy	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Infections and infestations Sepsis	17.0% 9/53 • Number of events 9 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Cardiac disorders Sinus bradycardia	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Small intestinal obstruction	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Typhlitis	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
General disorders Multi-organ failure	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Gastric hemorrhage	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.

Other adverse events

Other adverse events
Measure	Treatment (Chemotherapy) n=53 participants at risk Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Dasatinib: Given PO Doxorubicin: Given IV Etoposide: Given IV Imatinib Mesylate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Gastrointestinal disorders Abdominal pain	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Diarrhea	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
General disorders Edema limbs	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Blood and lymphatic system disorders Febrile neutropenia	5.7% 3/53 • Number of events 3 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Vascular disorders Hypertension	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Vascular disorders Hypotension	3.8% 2/53 • Number of events 2 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Gastrointestinal disorders Mucositis oral	9.4% 5/53 • Number of events 6 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.
Infections and infestations Sepsis	1.9% 1/53 • Number of events 1 • From the time patient signs consent through 30 days following discontinuation of study treatment, or until patient receives alternative anti-cancer therapy, whichever date comes first, up to 2 years.

Additional Information

Ryan Cassaday, MD

University of Washington

Phone: 2066061202

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place