Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients
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Purpose
The goal of the Phase 1 part of this study is to find the highest tolerable dose of Lintuzumab-Ac225 that can be given with cytarabine to patients with acute myeloid leukemia (AML).
The goal of the Phase 2 part of this study is to learn if Lintuzumab-Ac225 and cytarabine can control AML. The safety of this drug combination will also be studied.
Lintuzumab-Ac225 is designed to deliver radiation therapy directly inside leukemia cells without giving any radiation to the surrounding normal cells
Cytarabine is designed to insert itself into DNA (genetic material) of cancer cells and stop the DNA from repairing itself.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: Cytarabine Biological: Lintuzumab-Ac225 Drug: Lasix Drug: Spironolactone |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
- Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 52 days ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 24 |
| Study Start Date: | October 2012 |
| Estimated Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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Experimental: Cytarabine + Lintuzumab-Ac225
Cytarabine 20 mg subcutaneously every 12 hours Days 1 to 10 of every cycle. Starting dose level 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4 - 7 days after 1 cycle of low dose cytarabine and the second fraction administered 4-7 days after the first fraction, followed by up to 11 more cycles. Lasix 40 mg by mouth (po) daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose. Spironolactone, 25 mg po daily, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
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Drug: Cytarabine
Low dose cytarabine administered at 20 mg subcutaneously every 12 hours for the first 10 days (Days 1 to 10) of every cycle. Cycle 1 can last up to 52 days (depending on the schedule of study drug dosing) in order to allow for recovery from Lintuzumab-Ac225. Cycles 2-12 will last 28 days each.
Other Names:
Biological: Lintuzumab-Ac225
Starting dose level 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4 - 7 days after 1 cycle of low dose cytarabine and the second fraction administered 4-7 days after the first fraction, followed by up to 11 more cycles.
Other Name: Lintuzumab
Drug: Lasix
40 mg by mouth daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose.
Other Name: furosemide
Drug: Spironolactone
25 mg by mouth daily, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
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Detailed Description:
Study Groups:
If found to be eligible to take part in this study, participants will be assigned to a study group based on when joining the study. Up to 4 groups of up to 6 participants will be enrolled in the Phase I portion of the study, and up to 53 participants will be enrolled in Phase II.
If enrolled in the Phase I portion, the dose of Lintuzumab-Ac225 received will depend on when participant joined this study. The first group of participants will receive the lowest dose level of Lintuzumab-Ac225. Each new group will receive a higher dose of Lintuzumab-Ac225 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of Lintuzumab-Ac225 is found.
If enrolled in the Phase II portion, participant will receive Lintuzumab-Ac225 at the highest dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of cytarabine.
Study Drug Administration:
Participants will receive cytarabine as an injection under the skin. This is called a subcutaneous injection. During the first office visit, participant or a caregiver will be taught to give these injections at home. Participant will get cytarabine injections 2 times each day during Days 1-10 of each study cycle. Cycle 1 may last up to 52 days and will depend on how participant recovers from the Lintuzumab-Ac225. All other cycles will be 28 days.
Participant will receive Lintuzumab-Ac225 by vein over 15-30 minutes at a time point about 4 to 7 days after your last dose of cytarabine in Cycle 1. Participant will receive it a second time about 4 to 7 days after that.
One (1) day before the second dose of Lintuzumab-Ac225, participant will begin taking lasix (furosemide) by mouth every day for 10 days. Furosemide is taken to prevent possible damage to the kidneys.
One (1) day after last dose of furosemide, participant will begin taking spironolactone by mouth every day for up to 1 year. It is also taken to prevent possible kidney damage.
Eligibility| Ages Eligible for Study: | 60 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Untreated acute myelogenous leukemia (AML), including patients with an antecedent hematologic disorder or secondary disease. Patients with prior myelodysplastic syndromes (MDS) may have received therapy with immunomodulatory agents or hypomethylating agents for this diagnosis. patients with other prior cancer diagnoses are allowed as long as they ahve no measurable disease are not undergoing active therapy, and have a life expectancy of greater than or equal 4 months.
- Patients age greater than or equal to 60 years who: a. Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or b. Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or chemoradiation therapy (XRT), abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with Internal tandem duplications of Flt3 (Flt3-ITD), or presenting white blood count (WBC) greater than 100K, or c. Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g. anthracycline and infusional cytarabine given as 7+3); or d. Any patient age greater than or equal to 70 years.
- Blast count greater than or equal to 20 percent (World Health Organization (WHO) criteria)
- Greater than 25 percent of blasts must be CD33 positive.
- Creatinine less than 2.0 mg/dl
- Estimated creatinine clearance greater than or equal to 50ml/min.
- Bilirubin less than or equal to 2.0 mg/dl; aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) less than or equal to 2.5 times the upper limits of normal (ULN).
- Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 3.
Exclusion Criteria:
- Patients with acute promyelocytic leukemia.
- Treatment with chemotherapy or biologic therapy within 3 weeks, except for hydroxyurea, which must be discontinued prior to treatment on study
- Treatment with radiation within 6 weeks
- Active serious infections uncontrolled by antibiotics
- Active malignancy within 2 years of entry, except previously treated non-melanoma skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of progressive disease based on prostate-specific antigen (PSA) levels and are not on active therapy
- Clinically significant cardiac or pulmonary disease
- Active central nervous system (CNS) leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
- Psychiatric disorder that would preclude study participation
Contacts and Locations| Contact: Farhad Ravandi-Kashani, MD | 713-745-0394 |
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: Farhad Ravandi-Kashani, MD | |
| Study Chair: | Farhad Ravandi-Kashani, MD | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01756677 History of Changes |
| Other Study ID Numbers: | 2012-0434, API-01 |
| Study First Received: | December 20, 2012 |
| Last Updated: | December 20, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by M.D. Anderson Cancer Center:
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Cytarabine Lintuzumab-Ac225 ACTINIUM-225 HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195 Alpha-Particle-Emitting Immunoconjugates |
Additional relevant MeSH terms:
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Leukemia Neoplasms by Histologic Type Neoplasms Cytarabine Antibodies, Monoclonal Furosemide Spironolactone Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Sodium Potassium Chloride Symporter Inhibitors Membrane Transport Modulators Diuretics Natriuretic Agents Cardiovascular Agents Aldosterone Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists |
ClinicalTrials.gov processed this record on May 21, 2013