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Plerixafor

Clofarabine

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Plerixafor 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Phase II: Plerixafor at the highest dose tolerated in Phase I.

Plerixafor was dose-escalated in a 3+3 design, starting at 240 mcg/kg, and proceeding to dose levels of 320 mcg/kg, and 400 mcg/kg.

Starting at 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before a 1 hour (+/- 30 minutes) IV administration of Clofarabine

Fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Jan A. Burger, MD

The goal of Part 1 of this clinical research study is to learn about the safety of the combination of plerixafor and clofarabine when given to patients with previously untreated AML who are at least 60 years old.

The goal of Part 2 of this study is to learn if the combination of plerixafor and clofarabine can help to control previously untreated AML in patients who are at least 60 years old. Study was closed early and did not progress to Part 2.

The Study Drugs:

Plerixafor is designed to block a protein on cancer cells from attaching to cells in the bone marrow. This may allow cells in the bone marrow to be more effectively treated by chemotherapy.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 3 groups of up to 6 participants will be enrolled in the Part 1 portion of the study, and up to 48 participants will be enrolled in Part 2.

If you are enrolled in Part 1, the dose of plerixafor you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of plerixafor. Each new group will receive a higher dose of plerixafor than the group before it, if no intolerable side effects were seen.

If you are enrolled in Part 2, you will receive plerixafor at the highest dose that was tolerated in Part 1.

All participants will receive the same doses of clofarabine.

Study Drug Administration:

Cycles in this study are 28 days long, or possibly longer depending on your blood counts, any side effects, and the status of the disease.

On Days 1-5 of each cycle, you will receive plerixafor through a needle under the skin of your abdomen.

On Days 1-5 of each cycle, you will receive clofarabine by vein over about 1 hour. The dose will begin about 4 to 6 hours after the plerixafor injection. You will be watched for side effects while you receive clofarabine.

If the doctor thinks it is in your best interest, the dose level of plerixafor may be lowered.

Cycle 1 is called Induction. If the disease goes into remission (responds well) after the Induction cycle, you will start the Consolidation part of the study. In the Consolidation cycles, the schedule of administration of the drugs will be the same as in the Induction cycle, but the doses of clofarabine will be lower. If the disease does not go into remission after the Induction cycle, you will have a Reinduction cycle before you can begin the Consolidation part of the study. The goal of the Induction cycle and possible Reinduction cycle is to affect the bone marrow a certain way that may help control the disease. The goal of Consolidation is also to help control the disease.

Study Visits:

Induction (Cycle 1):

On Day 1 of Induction, blood (about ½ tablespoon each time) will be drawn for routine tests before the plerixafor injection and 3 times during the 8 hours after the injection.

On Days 2-5 of Induction, blood (about ½ tablespoon each time) will be drawn for routine tests before the plerixafor injection and again at 8 hours after the injection.

Starting in Week 2 of Induction, blood (about 2 tablespoons) will be drawn at least 2 times a week for routine tests.

You will have a bone marrow aspiration and/or biopsy to check the status of the disease on Day 21 of Induction and every 2 weeks after that, until the Induction cycle is over.

Reinduction:

If you have a Reinduction cycle, blood (about 2 tablespoons) will be drawn at least 2 times a week during Reinduction for routine tests. You will have a bone marrow aspiration and/or biopsy to check the status of the disease on Day 21 of Reinduction and every 2 weeks after that, until the Reinduction cycle is over.

Consolidation:

Blood (about 2 tablespoons) will be drawn 1 time a day for routine tests on Days 1-5 of Consolidation.

Starting in Week 2 of each Consolidation cycle, blood (about 2 tablespoons) will be drawn for routine tests every week for the rest of each Consolidation cycle.

You will have a bone marrow aspiration and/or biopsy to check the status of the disease anytime during Consolidation that the doctor decides it is needed.

Induction, Reinduction, and Consolidation:

The blood tests and/or bone marrow aspirations/biopsies may be performed more often than listed if the doctor thinks it is needed. Also, you will have an ECG anytime during the study if the doctor thinks it is needed.

Length of Study:

You may continue taking the study drugs for up to 5 Consolidation cycles, if the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the follow-up visits.

Follow-Up Visits:

At 1 and 3 months after you stop taking the study drugs:

* Blood (about 2 tablespoon) will be drawn for routine tests.
* If the doctor decides it is needed, you will have a bone marrow aspiration to check the status of the disease.

If the disease responds (if it goes into complete or partial remission), you will have follow-up visits every 3 months for up to 2 years after you stop taking the study drugs. The follow-up visits will stop if the disease gets worse, or if you start a new cancer therapy and the disease has not gotten worse. The following tests and procedures will be performed at the follow-up visits:

* Blood (about 2 tablespoon) will be drawn for routine tests.
* If the doctor decides it is needed, you will have a bone marrow aspiration to check the status of the disease.

This is an investigational study. Clofarabine is FDA approved and commercially available to treat acute lymphoblastic leukemia (ALL) in children after the disease has gotten worse a second time. Plerixafor is FDA approved to be given with G-CSF and is commercially available for use in moving stem cells into the bloodstream before a stem cell transplant to treat non-Hodgkin's lymphoma or multiple myeloma. The combination of clofarabine and plerixafor is investigational.

Up to 66 patients will take part in this study. All will be enrolled at MD Anderson.

Plerixafor and Clofarabine in Frontline Treatment of Elderly Patients With Acute Myelogenous Leukemia (AML)

Phase I/II Study of Plerixafor and Clofarabine in Previously Untreated Older (>/=60 Years) Adult Patients With Acute Myelogenous Leukemia (AML) With Two or More Unfavorable Prognostic Factors for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit

Dose limiting toxicity (DLT) consists of participants who developed DLT during maximum tolerated dose (MTD) estimation period where DLTs observed during dose escalation were used to develop MTD. The MTD is the highest dose level in which \<2 participants of 6 develop first cycle. DLT. Toxicity graded according to the NCI Common Toxicity Criteria Version 3.0. The timeframe to assess dose-limiting toxicities (DLT's) will be the first cycle of treatment, i.e. the first 4 weeks on study. The Plerixafor dose to be used in Phase II of the protocol is the highest dose at which no more than 1 of 6 patients experience a DLT in the Phase I part of the protocol or a lower dose selected at the end of dose escalation.

Response defined as Complete remission (CR): Disappearance all clinical +/or radiologic evidence disease. Neutrophil count \>/=1.0x10\^9/L \& platelet count \>/=100x10\^9/L, \& normal bone marrow differential (\</= 5% blasts). Complete Remission without Platelet Recovery (CRp): Peripheral blood \& bone marrow results as for CR, but with platelet counts of \<100x10\^9/L. Partial Remission (PR): Blood count recovery as for CR, but both decrease in marrow blasts \>50% \& not more than 6 to 25% abnormal cells in the marrow.

Overall response (OR) = Complete Remission (CR) + Partial Remission (PR) where response defined: Complete remission (CR): Disappearance all clinical +/or radiologic evidence disease. Neutrophil count \>/=1.0x109/L \& platelet count \>/=100x10\^9/L, \& normal bone marrow differential (\</= 5% blasts). Complete Remission without Platelet Recovery (CRp): Peripheral blood \& bone marrow results as for CR, but with platelet counts of \<100x10\^9/L. Partial Remission (PR): Blood count recovery as for CR, but both decrease in marrow blasts \>50% \& not more than 6 to 25% abnormal cells in the marrow. Treatment Failure: For purposes of efficacy analysis of remission, less than a CR, CRi, or PR categorized as Treatment Failure.

Genzyme, a Sanofi Company

M.D. Anderson Cancer Center

Plerixafor 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Plerixafor 240 mcg/kg + Clofarabine

Plerixafor 320 mcg/kg daily SQ injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Plerixafor 320 mcg/kg + Clofarabine

Plerixafor 400 mcg/kg daily SQ injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Plerixafor 400 mcg/kg + Clofarabine

Total

Age, Continuous

Range of Years

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

Early termination led to no subjects analyzed for later period outcomes.

Dr. Jan Burger, Associate Professor, Leukemia

Intent to treat population included all registered participants.

Number of Participants in Phase I With First Cycle Dose Limiting Toxicities (DLT) Observed

Two participants were not evaluable due to unrelated early death.

Participants' Response During First Part of Study

Study halted early without continuing to second part (Phase II). This outcome measure is to analyze the overall response during the Phase II portion of this study. The study was halted early and did not enroll any patients in the phase II portion. Therefore, there are Zero patients to analyze and no data to report.

Number of Participants With Overall Response During Second Part of Study

Plerixafor 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before hour intravenous (IV) administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Plerixafor and Clofarabine in Frontline Treatment of Elderly Patients With Acute Myelogenous Leukemia (AML)	NCT01160354	Acute Myelogeno...	Plerixafor Clofarabine	60 Years -	M.D. Anderson Cancer Center
Plerixafor and Clofarabine in Frontline Treatment of Elderly Patients With Acute Myelogenous Leukemia (AML)	NCT01160354	Acute Myelogeno...	Plerixafor Clofarabine	60 Years -	M.D. Anderson Cancer Center

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