Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia

NCT01088984 | Completed Phase 1 Results

• 2 other identifiers: C18083/20462010-020768-40
• Study Type: interventional
• Target: 43
• Locations: 12 countries
• Sites: 50

Brief Summary

The primary objective of phase 1 of this study is to establish the recommended phase II dose (RP2D). The primary objective of phase 2 of this study is to evaluate the safety and efficacy of bendamustine at the recommended pediatric dose for the treatment of pediatric patients with relapsed or refractory acute leukemia.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose (RP2D) of Bendamustine

  RP2D was determined by a traditional 3+3 dose escalation design, with the following restrictions: only doses of 60, 90, 120, and 150 mg/m\^2 were explored, and escalation to 150 mg/m\^2 would only occur if the 120 mg/m\^2 dose was deemed safe and pharmacokinetic data indicate subtherapeutic exposure as compared with adults. The first cohort was administered bendamustine at the 90 mg/m\^2 dose; de-escalation to the 60 mg/m\^2 dose would only occur if the starting dose led to dose-limiting toxicity (DLT) in 2 or more participants. A DLT was defined as any study drug-related nonhematologic adverse event (AE) that was grade 4 for toxicity by National Cancer Institute's Common Toxicity Criteria for AEs, version 4. In addition, grade 3 or above allergic reaction or skin rash were considered DLTs. Hematologic AEs were not considered DLTs. The dose level at which at least 2 of 3 or 2 of 6 participants had a DLT was considered as exceeding the RP2D. The RP2D was the dose 1 step below that level.

  Induction Cycle (21- to 35-day cycle)

• Overall Response Rate (ORR)

  ORR was calculated as follows: number of participants in the primary analysis set achieving a best overall response of complete remission without platelet recovery (CRp) or complete remission (CR), divided by the number of participants in the primary analysis set. The most positive response for each patient during the study was counted. The 95% CI was calculated using binomial parameter exact method. Response was determined by the investigator, and evaluated per Jeha et al, 2006: A CR required no evidence of circulating blasts or extramedullary disease, an M1 marrow (≤ 5% bone marrow blasts), and recovery of peripheral counts (platelets ≥ 100 × 10\^9/L and absolute neutrophil count ≥ 1.0 × 10\^9/L). A CR without platelet recovery (CRp) required all of the criteria for a CR with the exception of platelet recovery.

  Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles

Secondary Outcomes (7)

• Best Overall Tumor Response Rate

  At each treatment cycle (21 to 35 days), for a maximum of 12 cycles

• Best Overall Tumor Response Rate, by Phase

  At each treatment cycle (21 to 35 days), for a maximum of 12 cycles

• Duration of Response (DOR)

  At each treatment cycle (21 to 35 days), for a maximum of 12 cycles

• Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)

  Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.

• Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)

  Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.

Study Arms (1)

Bendamustine

EXPERIMENTAL

Bendamustine 90 or 120 mg/m\^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.

Drug: Bendamustine

Interventions

Bendamustine DRUG

Bendamustine

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The patient has histologically proven acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) that has relapsed or is refractory to the last regimen, and the patient is without alternative curative therapy.
• The patient's last myelosuppression therapy ended at least 2 weeks before the first dose of study drug.
• Nonhematologic acute toxic effects of prior therapy have resolved to grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
• The patient has adequate liver function with bilirubin values less than or equal to 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values less than or equal to 5 times the age-appropriate ULN.
• The patient has adequate renal function with serum creatinine values less than 2 times ULN.
• The patient has Karnofsky or Lansky performance status of 60 or greater. Patients older than 16 years of age will be scored according to the Karnofsky scale and patients 16 years of age or younger will be scored according to the Lansky scale.
• The patient may have had hematopoietic stem cell transplantation.
• Women of childbearing potential (not surgically sterile) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
• Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
• The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.

You may not qualify if:

• The patient has any active, uncontrolled systemic infection, severe concurrent disease, or symptomatic untreated central nervous system (CNS) involvement.
• The patient has evidence of active graft versus host disease.
• The patient has a known human immunodeficiency virus (HIV) infection.
• The patient has active hepatitis B or hepatitis C infection.
• The patient is a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study immediately.
• The patient has any serious uncontrolled medical or psychological disorder that would impair the ability of the patient to receive study drug.
• The patient has any condition that places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.
• The patient has received any other investigational agent within 30 days of study entry.
• The patient has known hypersensitivity to bendamustine or mannitol.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (50)

Teva Investigational Site 17

Orange, California, United States

Location

Teva Investigational Site 12

San Diego, California, United States

Location

Teva Investigational Site 10

St. Petersburg, Florida, United States

Location

Teva Investigational Site 8

Baltimore, Maryland, United States

Location

Teva Investigational Site 16

Boston, Massachusetts, United States

Location

Teva Investigational Site 9

Detroit, Michigan, United States

Location

Teva Investigational Site 1

Jackson, Mississippi, United States

Location

Teva Investigational Site 5

Kansas City, Missouri, United States

Location

Teva Investigational Site 14

St Louis, Missouri, United States

Location

Teva Investigational Site 15

New York, New York, United States

Location

Teva Investigational Site 18

Portland, Oregon, United States

Location

Teva Investigational Site 11

Hershey, Pennsylvania, United States

Location

Teva Investigational Site 7

Philadelphia, Pennsylvania, United States

Location

Teva Investigational Site 19

Memphis, Tennessee, United States

Location

Teva Investigational Site 3

Dallas, Texas, United States

Location

Teva Investigational Site 4

Fort Worth, Texas, United States

Location

Teva Investigational Site 13

Houston, Texas, United States

Location

Teva Investigational Site 2

Seattle, Washington, United States

Location

Teva Investigational Site 6

Milwaukee, Wisconsin, United States

Location

Teva Investigational Site 300

Herston, Australia

Location

Teva Investigational Site 301

Parkville, Australia

Location

Teva Investigational Site 302

Randwick, Australia

Location

Teva Investigational Site 520

Minsk, Belarus

Location

Teva Investigational Site 615

Barretos-SP, Brazil

Location

Teva Investigational Site 616

Caxias do Sul, Brazil

Location

Teva Investigational Site 613

Curitiba-PR, Brazil

Location

Teva Investigational Site 612

Porto Alegre, Brazil

Location

Teva Investigational Site 614

Porto Alegre, Brazil

Location

Teva Investigational Site 617

Sao Paulo-SP, Brazil

Location

Teva Investigational Site 610

São Paulo, Brazil

Location

Teva Investigational Site 611

São Paulo, Brazil

Location

Teva Investigational Site 100

Toronto, Canada

Location

Teva Investigational Site 501

Jerusalem, Israel

Location

Teva Investigational Site 503

Petah Tikva, Israel

Location

Teva Investigational Site 502

Ramat Gan, Israel

Location

Teva Investigational Site 603

Guadalajara, Mexico

Location

Teva Investigational Site 600

Mexico City, Mexico

Location

Teva Investigational Site 601

Mexico City, Mexico

Location

Teva Investigational Site 602

Monterrey, Mexico

Location

Teva Investigational Site 303

Auckland, New Zealand

Location

Teva Investigational Site 531

Bialystok, Poland

Location

Teva Investigational Site 530

Lublin, Poland

Location

Teva Investigational Site 532

Warsaw, Poland

Location

Teva Investigational Site 511

Moscow, Russia

Location

Teva Investigational Site 510

Saint Petersburg, Russia

Location

Teva Investigational Site 320

Singapore, Singapore

Location

Teva Investigational Site 330

Seoul, South Korea

Location

Teva Investigational Site 331

Seoul, South Korea

Location

Teva Investigational Site 332

Seoul, South Korea

Location

Teva Investigational Site 333

Seoul, South Korea

Location

Related Publications (1)

• Fraser C, Brown P, Megason G, Ahn HS, Cho B, Kirov I, Frankel L, Aplenc R, Bensen-Kennedy D, Munteanu M, Weaver J, Harker-Murray P. Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia: efficacy and tolerability. J Pediatr Hematol Oncol. 2014 May;36(4):e212-8. doi: 10.1097/MPH.0000000000000021.

  PMID: 24072240 BACKGROUND

MeSH Terms

Conditions

Leukemia

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Manager
• Organization: Teva Pharmaceuticals USA

clinicaltrialqueries@tevausa.com

1-866-384-5525

Study Officials

• Sponsor's Medical Expert

  Cephalon

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: March 18, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: May 23, 2016
• Results First Posted: October 1, 2014

Record last verified: 2016-04

Locations

SG (1); RU (2); US (19); IL (3); PL (3); BE (1); NZ (1); CA (1); KR (4); ME (4); BR (8); AU (3)