Ruxolitinib Phosphate in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Administration of Jakafi (Ruxolitinib) to Patients With Previously Untreated High-Risk Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): A Phase II Clinical Trial

This phase II trial studies how well ruxolitinib phosphate works in treating patients with previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Untreated Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Ruxolitinib Phosphate; Drug: Ruxolitinib

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the effect of ruxolitinib phosphate (ruxolitinib) in patients with high-risk chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who do not require anti-neoplastic therapy according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 recommendations and were either previously untreated or treated with Ibrutinib for less than 3 months and were deemed Ibrutinib intolerant:

Ia. On disease burden. Ib. The rate of complete response (CR) and partial response (PR) as assessed by the IWCLL 2008 response criteria.

SECONDARY OBJECTIVES:

I. To evaluate the time to next treatment of high-risk CLL/SLL who do not require anti-neoplastic therapy according to the IWCLL 2008 recommendations.

OUTLINE:

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID). Treatment continues for up to 3 years in the absence of disease progression or unacceptable toxicity. Treatment beyond 3 years may be permitted after discussion with the principal investigator.

After completion of study treatment, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. Subjects who are able to understand and sign an informed consent document.
2. Subjects 18 years of age or older.
3. Subjects must be diagnosed with CLL/SLL and do not meet the IWCLL criteria for treatment
4. Patients should be previously untreated or have only been treated with single agent ibrutinib therapy for a period of < 3 months and were deemed ibrutinib intolerant.
5. Patients whose expected time to CLL/SLL treatment, according to our nomogram posted on the leukemia protocol priority list, is four years of less.
6. Subjects with hemoglobin values at the screening visit equal to or greater than 12.0 g/dL.
7. Subjects with a platelet count of at least 100 x10^9 at the screening visit.
8. Subjects with an absolute neutrophil count (ANC) of equal to or higher than 0.5 x10^9 at the screening visit.
9. Subject who are willing to undergo a bone marrow aspiration and biopsy and CT scan for disease burden assessment.
10. Patient who are capable to return to MD Anderson Cancer Center (MDACC) for follow-up
11. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
12. Patient must be capable of swallowing the Ruxolotinib capsules (tablets).

Exclusion:

1. Females who are pregnant or are currently breastfeeding.
2. Subjects of childbearing potential who are unwilling to take appropriate precautions (throughout the study from screening including 30 days after discontinuation of the study drug) to avoid becoming pregnant or fathering a child. A) Females of non-childbearing potential are defined as women who (a) are equal to or greater than 55 years of age with history of amenorrhea for 1 year, OR (b) are surgically sterile for at least 3 months. B) For females of childbearing potential, or for males, appropriate precautions are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the subjects and their understanding confirmed: a) Double barrier methods; b) Condom with spermicide in conjunction with use of an intrauterine device (IUD); c) Condom with spermicide in conjunction with use of a diaphragm; d) Oral, injectable, or implanted contraceptives; e) Tubal ligation or vasectomy (surgical sterilization)
3. Subjects with recent history of inadequate bone marrow reserve as demonstrated by previous transfusions except for acute blood loss (e.g. surgery) in the month prior to screening.
4. Subjects with inadequate liver or renal function at screening and baseline visits: A) Alanine aminotransferase (ALT) > 2.5x Upper limit of normal (ULN). B) Modification of Diet in Renal Disease (MDRD) calculated GFR < 30 mL/min
5. Subjects with active uncontrolled infection or who are HIV positive (Subjects with acute infections requiring treatment should delay screening/enrollment until the course of therapy has been completed and the event is considered controlled).
6. Subjects with a history of or a current malignancy except for treated basal or squamous carcinomas of the skin completely resected.
7. Subjects with clinically significant uncontrolled cardiac disease.
8. Subjects being treated concurrently with any prohibited medications, including investigational medication, rifampin, St. John's wort, and potent CYP3A4 inhibitors (excluding ketoconazole) unless continuation of such medications are determined by the investigator to be in the best interest of the patient. Refer to protocol section 2.2.12 for more details.
9. Subjects who have previously received JAK inhibitor therapy
10. Subjects with active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
11. Subjects with any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol.
12. Subjects who have unknown transfusion history.
13. Patients who cannot comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (ruxolitinib phosphate); Patients receive ruxolitinib phosphate PO BID. Treatment continues for up to 3 years in the absence of disease progression or unacceptable toxicity. Treatment beyond 3 years may be permitted after discussion with the principal investigator.	Drug: Ruxolitinib Phosphate; Given PO; Other Names: Jakafi; INCB-18424 Phosphate; Drug: Ruxolitinib; Given PO; Other Names: INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With a Clinical Response	Clinical response will be assessed based on physical examination, complete blood count (CBC), a bone marrow aspiration, a whole body CT scan to be done at screening and 6 + 2 months in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines (Hallek et al., 2008)	Up to 6 months after initiation of therapy
Number of Participants With Change of Tumor Burden	Tumor burden will be assessed by bone marrow aspiration, whole body CT scan at screening and 6 months.	6 months after initiation of therapy
Participants With a Response	Response Rate is Complete Response (CR) or Partial Response (PR). CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes < 4000/ul, normocellular, <30% lymphocytes, no B-lymphoid nodules, Platelets > 100,000/ul, hemoglobin >11.0 g/dl and Neutrophils >1500/ul. PR is >/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count > 100,000/ul, Hemoglobin > 11 g/dl and Neutrophils >1500/ul or increase >/= 50% of all over base.	Up to 30 days
Time to Next Treatment	Number of months to subsequent therapy per patient.	Up to 30 days

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Zeev Estrov, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): April 29, 2020
• Study Completion (Actual): April 29, 2020

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimate): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): April 21, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors
• Other Study ID Numbers: 2015-0570 (Other Identifier: M D Anderson Cancer Center); NCI-2017-00478 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No