Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Etoposide

Cyclophosphamide

Etoposide phosphate

Clofarabine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Antimetabolites

Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m\^2, etoposide dosage from 75-100 mg/m\^2, cyclophosphamide dosage from 340-440 mg/m\^2.

Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously

Clofarabine 20-40 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle as the first of the three IV interventions administered. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

clofarabine

Etoposide 75-100 mg/m²/day 2 hour intravenous (IV) infusion daily for 5 days of a 28 day cycle following clofarabine therapy. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Cyclophosphamide 340-440 mg/m²/day as 30-60 minute intravenous (IV) infusion daily for 5 days of a 28 day cycle following the other two interventions. Maximum of 8 cycles given in both the phase 1 and phase 2 study periods.

Medical Monitor

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

The purpose of the phase 1 portion of this study was to determine if clofarabine added to a combination of etoposide and cyclophosphamide is safe in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). The purpose of the phase 2 portion of the study was to measure the effectiveness of the combination therapy in children with ALL.

A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.

A Phase 1/2 Dose-Escalation Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Pediatric Patients With Refractory or Relapsed Acute Leukemias.

The MTD was to be the highest dose level of clofarabine in combination with etoposide and cyclophosphamide that caused \<= 1 of 6 participants to experience a dose limiting toxicity (DLT) with the next higher dose level having at least 2 of 3 or 2 of 6 participants experiencing a DLT. The MTD would be used as the recommended phase 2 dose (RP2D). If the MTD could not be determined, then the target dose of clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 as taken by Cohort 5 was to become the RP2D.

The rating scale used is 0 = not the MTD, 1 = the MTD.

The number of participants in each cohort that had dose limiting toxicity is summarized. Toxicities were reviewed by an independent Data Safety Monitoring Board (DSMB) who determined if additional participants should be added to the cohort and the criteria for escalating to the next cohort.

Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with \<5% blasts, and platelet (plt)/ANC recovery: ≥75/ ≥0.75 \[x 10\^9/L\] 2) CR in absence of plt recovery (CRp): plt ≥20 to \<75 x 10\^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with \<5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.

Number of participants with AEs that occurred during treatment and follow-up period (45 days after last cycle). Drug-related AEs and SAEs were followed until resolved or mutually agreed by the investigator and Genzyme to discontinue reporting. AEs were classified by the investigator according to severity (graded using National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0) and relationship to study drug. The severity scale is:\> Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death related to AE

Response categories 1) complete remission (CR): without circulating blasts or extramedullary disease, bone marrow (BM) with \<5% blasts, and platelet (plt)/ANC recovery: ALL ≥75/ ≥0.75 \[x 10\^9/L\]; AML ≥100/ ≥1.0 \[x 10\^9/L\] 2) CR in absence of plt recovery (CRp): ALL plt ≥20 to \<75 x 10\^9/L; AML plt ≥20 to \<100 x 10\^9/L 3) partial remission (PR): no circulating blasts, appearance of normal hematopoietic progenitors, and either a BM with ≥5% and ≤25% blasts with recovery of plts/ANC or a BM with \<5% blasts not meeting CR/CRp definition 4) Overall remission (OR): CR+CRp 5) Any response: CR+CRp+PR.

The weeks between start of intervention and remission as assessed by the investigator in Phase 1. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.

Duration of response is the time from the first objective measurement of complete response (CR) or complete response with the absence of total platelet recovery (CRp) to the date of first objective documentation of disease relapse or death due to any cause, plus one day. For summary purposes, results are presented as weeks.

Event-free survival (EFS) is defined as the time from date of first administration of study interventions until the earliest of the following: date of death or date of first response assessment confirming relapse or date of final response assessment which fails to confirm response, plus one day. For summary purposes, results are presented as weeks.

Number of participants with event-free survival at four months post first dose of therapy. A participant is considered event-free if at month 4 they have not died or had a response assessment confirming a relapse.

Overall survival is defined as the time from date of first administration of study interventions until date of death, plus one day. For summary purposes, results are presented as weeks.

The weeks between start of intervention and remission as assessed by the investigator in Phase 2. Participants who had a complete remission (CR) or complete remission with the absence of total platelet recovery (CRp) are included.

Genzyme, a Sanofi Company

In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of adverse event tables.

Participants were treated with clofarabine 20 mg/m\^2, etoposide 75 mg/m\^2, and cyclophosphamide 340 mg/m\^2.

Phase 1 - Cohort 1

Participants were treated with clofarabine 20 mg/m\^2, etoposide 75 mg/m\^2, and cyclophosphamide 440 mg/m\^2.

Phase 1 - Cohort 2

Participants were treated with clofarabine 20 mg/m\^2, etoposide 100 mg/m\^2, and cyclophosphamide 440 mg/m\^2.

Phase 1 - Cohort 3

Participants were treated with clofarabine 30 mg/m\^2, etoposide 100 mg/m\^2, and cyclophosphamide 440 mg/m\^2.

Phase 1 - Cohort 4

Participants were treated with clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2, and cyclophosphamide 440 mg/m\^2.

Phase 1 - Cohort 5

All participants from Cohorts 1-5 in Phase 1

Phase 1 - Total

Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously.

Phase 2: Clofarabine, Etoposide, Cyclophosphamide

Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m\^2, etoposide dosage from 75-100 mg/m\^2, cyclophosphamide dosage from 340-440 mg/m\^2.

Phase 1: Clofarabine, Etoposide, Cyclophosphamide

Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously

Total

The two study phases were not designed to be reported in the aggregate.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Percent of leukemic blast cells based on bone marrow aspirate. The two study phases were not designed to be reported in the aggregate.

Percent Leukemic Blast Cells

Absolute Neutrophil Counts

White Blood Cell Counts

B cell

T cell

Unknown

not included (AML participants)

Applies to acute lymphoblastic leukemic (ALL) participants only. Acute myelogenous leukemic (AML) participants are not included. The two study phases were not designed to be reported in the aggregate.

Immunophenotype

1 regimen

2 regimens

3 regimens

Count of Previous Anti-Leukemic (non-transplant) Treatment Regimens

Transplants

No transplants

Participants with Previous Anti-Leukemic Transplant Regimens

The answer "Yes" indicates the number of participants who were refractory (unresponsive) to the most recent anti-leukemic treatment. The answer "No" represents participants who were not refractory. The two study phases were not designed to be reported in the aggregate.

Participants Who Were Refractory to the Most Recent Previous Anti-Leukemic Treatment

Baseline performance was rating using either the Karnofsky Performance Scale for participants greater than 10 years old, or the Lansky Performance Scale for participants 10 years or younger. Both scales range from 0-100 with 0 indicating dead or unresponsive and 100 indicating normal performance. The two study phases were not designed to be reported in the aggregate.

Participant Rating Using the Karnofsky/Lansky Performance Status Scale

Genzyme Medical Information

Maximum Tolerated Dose (MTD) in Phase 1

Participants With Dose Limiting Toxicity in Phase 1

At least one AE

At least one AE related to clofarabine

At least one serious AE

At least one serious AE related to clofarabine

Discontinued study due to AE

Died

AE with the worst grade of: 1

AE with the worst grade of: 2

AE with the worst grade of: 3

AE with the worst grade of: 4

AE with the worst grade of: 5

Summary of Participants With Adverse Events (AEs) in Phase 1

Complete remission (CR)

Complete remission/absence total platelet recovery

Partial remission (PR)

Overall remission (OR)

Any response (CR+CRp+PR)

Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 1

Participants in phase 1 who had an overall remission.

Time to Remission for Participants Who Had a Response in Phase 1

Phase 1 participants who achieved overall remission. Data are censored at date of last known follow-up visit.

Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 1

All phase 1 participants. Data are censored at date of last known follow-up visit.

Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 1

Number of Participants With 4-month Event Free Survival in Phase 1

Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 1

Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 2

Summary of Participants With Adverse Events (AEs) in Phase 2

Participants in phase 2 who had an overall remission.

Time to Remission for Participants Who Had a Response in Phase 2

Phase 2 participants who achieved overall remission. Data are censored at date of last known follow-up visit.

Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 2

All phase 2 participants. Data are censored at date of last known follow-up visit.

Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 2

Number of Participants With 4-month Event Free Survival in Phase 2

Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 2

Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m\^2, etoposide dosage from 75-100 mg/m\^2, cyclophosphamide dosage from 340-440 mg/m\^2.\> Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously

Spots Global Cancer Trial Database for clo218

Every month we try and update this database with for clo218 cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for clo218

Every month we try and update this database with for clo218 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for clo218 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.