Clinical trial

A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts

Name

CDR0000257122

Description

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar trihydrochloride, a modulator of multidrug resistance (MDR), may help daunorubicin and cytarabine kill more cancer cells by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or anemia. PURPOSE: This randomized phase III trial is studying how well giving zosuquidar trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or anemia that has not responded to previous treatment.

Trial arms

Trial start

2002-09-17

Estimated PCD

2009-06-01

Phase

Early phase I

Treatment

filgrastim

250 μg/m2/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to \> 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.

Arms:

Placebo, Zosuquidar

Other names:

Neupogen, recombinant-methionyl human granulocyte-colony stimulating factor,, granulocyte colony-stimulating factor, r-metHuG-CSF

sargramostim

5 μg/kg/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to \> 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.

Arms:

Placebo, Zosuquidar

Other names:

Granulocyte-macrophage colony stimulating factor, rHu GM-CSF,, Leukine, NSC # 617589

cytarabine

100 mg/m²/day by continuous intravenous infusion for 7 days (days 1-7).

Arms:

Placebo, Zosuquidar

Other names:

Cytosar-U, Ara-C, Arabinosyl, cytosine arabinoside.

daunorubicin hydrochloride

45 mg/m²/day by 10 - 15 minute intravenous infusion for 3 days (days 1, 2, and 3).

Arms:

Placebo, Zosuquidar

Other names:

Daunomycin, Rubidomycin, Cerubidine.

zosuquidar trihydrochloride

Zosuquidar 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3. The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3.

Arms:

Zosuquidar

Other names:

Multi drug resistance modulator, MDR, LY335979

Placebo

Placebo 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3. The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3. Placebo consisted of a 1:1000 dilution of Infuvite, appropriately colored.

Arms:

Placebo

Other names:

Baxter Infuvite Adult

Size

449

Primary endpoint

Overall Survival (OS)

Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter

Eligibility criteria

Inclusion Criteria: One of the following disorders: * Acute myeloid leukemia (AML), defined as \>30% myeloblasts on the marrow aspirate or peripheral blood differential and any French-American-British (FAB) subtype except M3 (i.e., acute promyelocytic leukemia) * Refractory anemia with excess blasts (RAEB), defined as 11-20% myeloblasts on bone marrow aspirate or peripheral blood differential, provided there are other criteria for high-risk disease * Refractory anemia with excess blasts in transformation (RAEB-T), defined as 21-30% myeloblasts on bone marrow aspirate or peripheral blood differential * Participants may have secondary AML * Age greater than 60 years * ECOG performance status of 0 to 3 * Total serum bilirubin \< 3 mg/dL * Serum creatinine \< 2 mg/dL * Cardiac ejection fraction of \> 45% Exclusion Criteria: * Blastic transformation of chronic myelogenous leukemia * CNS leukemia * Prior chemotherapy for AML, with the exception of hydroxyurea * For women: pregnant or breast feeding * Other malignancy for which participant is currently receiving treatment * Concurrent treatment with other colony-stimulating factors

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 449, 'type': 'ACTUAL'}}

Updated at

2023-07-05

1 organization

2 products

4 drugs

2 indications

Organization

Eastern Cooperative Oncology Group

Drug

Filgrastim

Indication

Leukemia