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An Open-label, Phase Ib Study of IPI-145 in Combination With Bendamustine, Rituximab or Bendamustine/Rituximab in Select Subjects With Lymphoma or Chronic Lymphocytic Leukemia


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Lymphoma, Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, T-cell Lymphoma

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Trial Information

An Open-label, Phase Ib Study of IPI-145 in Combination With Bendamustine, Rituximab or Bendamustine/Rituximab in Select Subjects With Lymphoma or Chronic Lymphocytic Leukemia


This trial consists of three parallel arms. For each treatment arm, a 3+3 dose escalation
design will be applied in 3-6 subject cohorts until the maximum tolerated dose of IPI-145
when given with rituximab (Arm 1), or in combination with rituximab and bendamustine (Arm 2)
or with bendamustine (Arm 3) is determined. The population during dose escalation will be
limited to subjects diagnosed with NHL with at least one prior anticancer treatment. Once
the MTD of each arm has been determined, the arms will move on to a dose expansion phase.
During the dose expansion phase, each treatment arm will enroll to population specific
cohorts. All subjects must have had at least one prior anticancer treatment. The dose
expansion cohorts are:

Arm 1: Cohort A - CLL, Cohort B - CD20+ NHL; Arm 2: Cohort A - CLL, Cohort B - CD20+
NHL; Arm 3: Cohort C - T-Cell Lymphoma


Inclusion Criteria:



1. Dose Escalation Phase Arm 1 and Arm 2: Limited to subjects diagnosed with low grade
CD-20 positive B-Cell NHL with at least one prior anticancer treatment.

Arm 3: Limited to subjects with a diagnosis of NHL with at least one prior anticancer
treatment.

2. Dose Expansion Phase Arm 1 Cohort A: Limited to subjects with CD-20 positive CLL
with at least one prior anticancer treatment.

Arm 1 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at
least one prior anticancer treatment.

Arm 2 Cohort A: Limited to subjects with CD-20 positive CLL with at least one prior
anticancer treatment.

Arm 2 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at
least one prior anticancer treatment.

Arm 3 Cohort C: Limited to subjects with T-cell lymphoma who have had at least one
prior anticancer treatment.

3. Disease status requirement:

- CLL subjects: symptomatic disease that mandate treatment;

- Indolent NHL subjects: symptomatic disease requiring treatment according to the
clinical judgment of the investigator;

- Other lymphoma subjects: disease requiring treatment according to the judgment
of the investigator.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤2.

5. Subject must have measurable disease using the disease-specific response criteria for
NHL, CLL or T-Cell Lymphoma.

6. Age ≥ 18 years.

7. Subject has recovered from all clinically significant toxicities related to prior
antineoplastic therapies with the exception of alopecia and bone marrow and organ
functions.

8. Adequate organ system function ≤2 weeks prior to Day 1, defined as follows:

- Absolute neutrophil count (ANC) ≥1.0 x 109/L unless related to underlying CLL or
indolent NHL bone marrow involvement, and then ANC ≥500 x 109/L permitted.

- Platelets ≥100 x 109/L unless related to underlying CLL or indolent NHL bone
marrow involvement, and then platelets ≥75 x 109/L permitted.

Patients receiving IPI-145 plus rituximab with bone marrow involvement may enroll
with platelets ≥40 x 109/L.

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 x ULN
and total bilirubin ≤1.5 times the upper limit of normal (ULN) (except for
subjects with Gilbert's disease)

- Serum creatinine ≤1.5 x ULN

9. Life expectancy of ≥12 weeks.

10. Women of child-bearing potential (WCBP) must have a negative serum or urine pregnancy
test.

11. Ability to understand the nature of this study and give written informed consent.

Exclusion Criteria:

1. Prior allogeneic hematopoietic stem cell transplant (HSCT).

2. Prior autologous transplant or radioimmunotherapy ≤6 months prior to the first dose
of trial treatment.

3. Subject has a high grade lymphoma such as Burkitt's, lymphoblastic or small
non-cleaved cell lymphomas. Subjects with intermediate grade lymphoma (such as
diffuse large B-cell lymphoma) are eligible.

4. Subjects with diffuse B-cell lymphoma must either not be eligible for autologous bone
marrow transplant (BMT) or relapsed after autologous BMT.

5. More than three previous cytotoxic chemotherapy regimens for subjects treated on arms
containing bendamustine.

6. Subjects who have had a severe allergic or anaphylactic reaction to any humanized or
murine monoclonal antibodies.

7. Chemotherapy, cancer immunosuppressive therapy, growth factors (except
erythropoietin), radiation therapy (other than whole brain irradiation [WBI]) surgery
or ablative therapy or investigational drugs/devices ≤28 days before first dose of
trial treatment.

8. Subjects receiving high doses of corticosteroids must have been tapered to a stable
dose at least 7 days before the first dose of trial treatment.

9. Tyrosine kinase inhibitor within 7 days prior to the first dose of trial treatment.

10. Subjects with overt leptomeningeal leukemia or central nervous system (CNS) lymphoma.
Subjects must be free of CNS disease for a minimum of 2 months. Subjects with
symptoms of CNS disease must have a negative diagnostic lumbar puncture prior to
study enrollment.

11. Subjects with a history of stroke, unstable angina, myocardial infarction, or
ventricular arrhythmia requiring medication or mechanical control within the last 6
months.

12. Baseline QTcF >480 ms. Note: This criterion does not apply to subjects with a left
bundle branch block.

Exclusion Criteria:

13. Subjects who have had a venous thromboembolic event requiring anticoagulation and who
meet any of the following criteria:

- Have been on a stable dose of anticoagulation for <1 month.

- Have had a Grade 2, 3 or 4 hemorrhages in the last 30 days.

- Are experiencing continued symptoms for their venous thromboembolic event.

14. Subjects with a history of liver disease as a result of alcohol abuse, chronic
hepatitis, or other chronic liver disease (other than metastatic disease to the
liver).

15. Subjects with positive HBsAg, HBcAb or HCV are excluded.

16. Subjects with a history of tuberculosis within the preceding two years.

17. Prior surgery affecting drug absorption or any gastrointestinal dysfunction that
could alter drug absorption.

18. Subjects with a known hypersensitivity to bendamustine or rituximab.

19. Presence of active infection within 72 hours of treatment. Subjects with ongoing use
of prophylactic antibiotics are eligible as long as there is no evidence of active
infection and the antibiotic is not included on the list of prohibited medications.

20. Known diagnosis of human immunodeficiency virus (HIV).

21. Concurrent administration of medications or foods that are strong or moderate
inhibitors or inducers of CYP3A.

22. Women who are pregnant or lactating.

23. Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.

24. Concurrent condition that in the investigator's opinion would jeopardize compliance
with the protocol or would impart excessive risk associated with study participation
that would make it inappropriate for the subject to be enrolled.

25. Inability or unwillingness to comply with study and/or follow-up procedures outlined
in the protocol.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tolerability and Safety

Outcome Description:

To determine the tolerability, initial safety profile and MTD of IPI-145 in combination with the regimens rituximab, bendamustine/rituximab, or bendamustine by assessing subjects' adverse events, vital signs, and lab values.

Outcome Time Frame:

Up to 12 months

Safety Issue:

Yes

Principal Investigator

Ian Flinn, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

SCRI

Authority:

United States: Food and Drug Administration

Study ID:

SCRI HEMREF 34

NCT ID:

NCT01871675

Start Date:

May 2013

Completion Date:

June 2015

Related Keywords:

  • Lymphoma
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
  • T-Cell Lymphoma
  • Lymphoma
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
  • T-cell Lymphoma
  • Rituxan
  • Bendamustine
  • Hematologic Malignancy
  • Relapsed
  • Refractory
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Hematologic Neoplasms

Name

Location

Tennessee Oncology, PLLCClarksville, Tennessee  37043