Clinical Trial: Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized Phase II Trial of Timed Sequential Cytosine Arabinoside (Ara-C) With and Without the Checkpoint Kinase 1 (CHK1) Inhibitor MK-8776 in Adults With Relapsed AML

Brief Summary: This randomized phase II trial studies how well cytarabine with or without SCH 900776 works in treating adult patients with relapsed acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. SCH 900776 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cytarabine is more effective with or without SCH 900776 in treating acute myeloid leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the rates of complete remission (CR) plus CR with incomplete recovery (CRi) achieved with cytosine arabinoside (ara-C) (cytarabine) plus the checkpoint kinase 1 (CHK1) inhibitor MK-8776 (Chk1 inhibitor SCH 900776) vs. ara-C alone for adults (ages 18-75) with relapsed acute myelogenous leukemia (AML).

SECONDARY OBJECTIVES:

I. To evaluate and compare the toxicities of ara-C + MK-8776 vs. ara-C alone. II. To determine the disease free and overall survival of those achieving response to treatment.

III. To determine the impact of MK-8776 on AML blast cell deoxyribonucleic acid (DNA) repair protein expression profiles and correlate the expression profiles with CR/CRi in response to ara-C + MK-8776 vs. ara-C alone.

IV. To evaluate and compare the amount of DNA damage induced in AML blasts by ara-C + MK-8776 vs. ara-C.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cytarabine intravenously (IV) continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12.

ARM B: Patients receive cytarabine as in Arm A.

In both arms, courses may repeat every 28 days.

After completion of study treatment, patients are followed up periodically.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Response Rate(CR/CRi) Rate [ Time Frame: Up to 3 years ]

For descriptive purposes, the CR/CRi (complete response/Complete response with incomplete blood count recovery) rate will be reported at the end of the study separately for Arm A and Arm B. Responses are following definitions consistent with those published by Dohner H, Estey EH, Amadori S, et al. CR is defined as Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blasts in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. CRi: All CR criteria except for residual neutropenia (ANC < 1000/μL)


Original Primary Outcome: Complete response (CR/CRi) rate [ Time Frame: Up to 3 years ]

For descriptive purposes, the CR/CRi rate will be reported at the end of the study separately for Arm A and Arm B with exact binomial 95% confidence intervals. The final analysis will be by an exact Cochrane-Mantel-Haenszel test, which tests for an overall treatment difference while adjusting for disease subgroup. The primary analysis will conclude a significant benefit for Arm A over Arm B if the one-sided p value is less than 0.10.


Current Secondary Outcome:

Original Secondary Outcome:

  • Overall toxicity rate [ Time Frame: Up to 3 years ]
    Toxicity rate is reported for each arm with exact binomial 95% confidence intervals.
  • Rate of each specific toxicity [ Time Frame: Up to 3 years ]
    Toxicity rate is reported for each arm with exact binomial 95% confidence intervals.
  • AML blast cell DNA repair protein expression profiles [ Time Frame: Up to day 4 ]
    Will be summarized with descriptive statistics by CR/CRi in response to treatment. T tests or Wilcoxon rank sum tests will be used to describe differences in expression values between patients who do and do not achieve a CR/CRi, separately for each treatment arm. Further exploration of differences may be pursued with regression models that include interactions between treatment arm and response.
  • DNA damage induced in AML blasts [ Time Frame: Up to day 4 ]
    Will be summarized using descriptive statistics. Differences between treatment arms may be further described with a Wilcoxon rank sum test, or a Chi-square test, if the amount of DNA damage is categorized.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 3, 2013
Date Started: May 2013
Date Completion:
Last Updated: July 20, 2016
Last Verified: July 2016