Decitabine Followed by Clofarabine, Idarubicin, and Cytarabine in Acute Leukemia

NCT01794702 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2012-1064NCI-2013-00548
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of Phase I of this clinical research study is find the highest tolerable dose of clofarabine that can be given with decitabine, idarubicin, and cytarabine to patients with acute leukemia. The goal of Phase II of this study is to learn if decitabine followed by the combination of clofarabine, idarubicin, and cytarabine can help to control acute leukemia. The safety of this drug combination will also be studied. Decitabine and idarubicin are designed to damage the DNA (the genetic material of cells). This may cause cancer cells to die. Clofarabine is designed to interfere with the growth and development of cancer cells. Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.

Conditions

Leukemia

Keywords

Leukemia; Acute Leukemia; Acute myelogenous leukemia; AML; Acute lymphoblastic leukemia; ALL; Maximum Tolerated Dose; MTD; Response Rate; Decitabine; Dacogen; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Clofarabine

  Maximum tolerated dose (MTD) defined as the highest dose schedule in which 6 patients were treated with at most 1 experiencing a dose-limiting toxicity (DLT). Clofarabine 15 mg/m2 IV over approximately 1 hour daily (number of days selected based on Phase I portion).

  After second, 33 day cycle

• Number of Participants With a Response

  Primary endpoint is overall response defined as the best response either complete response, complete remission without platelet recovery, or complete remission without incomplete blood count recovery within 56 days.

  56 days

Secondary Outcomes (2)

• To Determine the Disease-free Survival (DFS).

  Up to 2 years after participants off study date

• Overall Survival

  Up to 2 years after participants off study date

Study Arms (1)

Clofarabine + Cytarabine + Decitabine + Idarubicin

EXPERIMENTAL

Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10) Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion). Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10)

Drug: Decitabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Clofarabine

Interventions

Decitabine DRUG

Phase I and II - 20 mg/m2 by vein daily for 5 days (days 1-5)

Also known as: Dacogen

Clofarabine + Cytarabine + Decitabine + Idarubicin

Idarubicin DRUG

Phase I and II - 10 mg/m2 by vein daily for 3 days (days 6-8)

Also known as: Idamycin

Clofarabine + Cytarabine + Decitabine + Idarubicin

Cytarabine DRUG

Phase I and II - 1 g/m2 by vein daily for 5 days (days 6-10)

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Clofarabine + Cytarabine + Decitabine + Idarubicin

Clofarabine DRUG

Phase I Starting Dose - 15 mg/m2 by vein daily for 4 days (days 6-9) Phase II Starting Dose - Maximum tolerated dose from Phase I (number of days selected based on Phase I portion).

Also known as: Clofarex, Clolar

Clofarabine + Cytarabine + Decitabine + Idarubicin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Sign an IRB-approved informed consent document.
• Age \>/= 18 years and \<65 years.
• Diagnosis of AML \[other than acute promyelocytic leukemia\] with refractory/relapsed disease (Patients must be primary refractory, in relapse 1, or in relapse 2). NOTE: Patients with AML arising from prior MDS or MPN would be eligible even if they have not received treatment for the AML. NOTE: Patients with relapsed/refractory ALL would also be eligible for the phase II part of the study. NOTE: Use of hydroxyurea and/or up to 4 doses of cytarabine, for emergent cytoreduction is allowed
• ECOG performance status of \</=2 at study entry.
• Organ function as defined below (unless due to leukemia):Serum creatinine \</= 3 mg/dL;Total bilirubin \</= 2.5 mg/dL; ALT (SGPT) \</= 3 x ULN or \</= 5 x ULN if related to disease
• Cardiac ejection fraction ≥ 40% (by either cardiac ECHO or MUGA scan)
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.

You may not qualify if:

• Breast feeding women
• Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
• Patients with active secondary malignancy will not be eligible unless approved by the PI.
• NOTE: Prior therapy with decitabine, clofarabine, idarubicin, or cytarabine is allowed, unless the prior therapy is identical to the schema/schedule proposed in this study

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Decitabine; Idarubicin; Cytarabine; Clofarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Nitin Jain, MD./Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

njain@mdanderson.org

713-745-6080

Study Officials

• Nitin Jain, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Starting with Dose level 1, the participants were enrolled by cohort of 3. Once the DLT assessment is completed, another cohort of 3 patients will be enrolled. If at any time, we see more than 30% patients experiencing DLT, we will de-escalate to dose level (-1). Period 1: Dose level 1 Clofarabine 15mg/m\^2 daily x 4 days (days 6-9) Period 2: Dose level-1 Clofarabine 15mg/m\^2 daily x 3 days (days 6-8)

Study Record Dates

• First Submitted: February 15, 2013
• First Posted: February 20, 2013
• Study Start: February 20, 2013
• Primary Completion: January 11, 2018
• Study Completion: January 11, 2018
• Last Updated: May 30, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-05

Locations

US (1)