Back to results

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Primary Purpose

Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alvocidib Hydrochloride

Cyclophosphamide

Diagnostic Laboratory Biomarker Analysis

Pharmacological Study

Rituximab

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic leukemia* (PLL) arising from CLL
- Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point since initial diagnosis of CLL
- Patients must have B-cells that co-express CD5 with CD19 or CD20
- Patients who do not have dim sIg or CD23 expression on their leukemia cells should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle cell lymphoma
To be considered high risk, patients must meet the following criteria:
- At least 1 of the following:
  - 17p deletion
  - 11q deletion
  - Un-mutated IgV_H (≥ 98% homology)
  - Age > 70 years
  - B_2M > 4
- AND at least 1 of the following:
  - Progressive or marked splenomegaly and/or lymphadenopathy
  - Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/mm^3)
  - Weight loss exceeding 10% of body weight over preceding 6 months
  - NCI grade 2 or 3 fatigue
  - Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection
  - Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of < 6 months
No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes)
- No requirement for chronic corticosteroids
ECOG performance status 0-2
Creatinine ≤ 2.0 mg/dL
Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease infiltration of the liver
AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver
Negative pregnancy test
Not pregnant or nursing
Fertile patients must use effective contraception
No secondary or other malignancy that will limit survival to < 2 years
No uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication
No active hepatitis B infection
No known G6PD deficiency
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used in this study
No prior alvocidib
No prior purine analog therapy
No more than 1 prior treatment with a biologic or alkylating agent
No other concurrent investigational agents

Sites / Locations

Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rituximab, cyclophosphamide, alvocidib)

Arm Description

Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).

Outcomes

Primary Outcome Measures

Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab

Determined using the CTEP Active Version of the CTCAE.

Treatment related adverse events assessed using the CTEP Active Version of the CTCAE

Secondary Outcome Measures

Full Information

NCT ID

NCT01076556

First Posted

February 25, 2010

Last Updated

November 10, 2015

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01076556

Brief Title

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Official Title

A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Study Start Date

April 2010 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

This phase I trial is studying the side effects and the best dose of alvocidib when given together with cyclophosphamide and rituximab in treating patients with high risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Other find cancer cells and help kill them or carry cancer-killing substances to them. Giving cyclophosphamide, alvocidib, and rituximab together may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the dose-limiting toxicity and maximum-tolerated dose of treatment with cyclophosphamide, alvocidib, and rituximab in patients with high-risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. II. To determine the feasibility of administering this regimen as an outpatient regimen in these patients. SECONDARY OBJECTIVES: I. To determine the complete response rate, partial response rate, and minimal-residual disease-negative response rate in patients treated with this regimen. II. To determine the pharmacokinetics of alvocidib and dexamethasone as part of this regimen. III. To determine the immunologic effects of this regimen as measured by serial T-cell and NK-cell number, T-cell function, and immunoglobulin levels. OUTLINE: This is a dose-escalation study of alvocidib. Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies. After completion of study treatment, patients are followed up for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage I Small Lymphocytic Lymphoma, Stage II Chronic Lymphocytic Leukemia, Stage II Small Lymphocytic Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Small Lymphocytic Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (rituximab, cyclophosphamide, alvocidib)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Alvocidib Hydrochloride

Other Intervention Name(s)

4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis-, Flavopiridol Hydrochloride, HL-275, HMR 1275, L-86-8275, L-868275, MDL 107,826A, MDL-107826A

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Diagnostic Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

Pharmacological Study

Intervention Description

Correlative studies

Intervention Type

Biological

Intervention Name(s)

Rituximab

Other Intervention Name(s)

BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar BI 695500, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, RTXM83

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab

Description

Determined using the CTEP Active Version of the CTCAE.

Time Frame

21 days

Title

Treatment related adverse events assessed using the CTEP Active Version of the CTCAE

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic leukemia* (PLL) arising from CLL Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point since initial diagnosis of CLL Patients must have B-cells that co-express CD5 with CD19 or CD20 Patients who do not have dim sIg or CD23 expression on their leukemia cells should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle cell lymphoma To be considered high risk, patients must meet the following criteria: At least 1 of the following: 17p deletion 11q deletion Un-mutated IgV_H (≥ 98% homology) Age > 70 years B_2M > 4 AND at least 1 of the following: Progressive or marked splenomegaly and/or lymphadenopathy Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/mm^3) Weight loss exceeding 10% of body weight over preceding 6 months NCI grade 2 or 3 fatigue Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of < 6 months No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes) No requirement for chronic corticosteroids ECOG performance status 0-2 Creatinine ≤ 2.0 mg/dL Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease infiltration of the liver AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver Negative pregnancy test Not pregnant or nursing Fertile patients must use effective contraception No secondary or other malignancy that will limit survival to < 2 years No uncontrolled concurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situations that would limit compliance with study requirements No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication No active hepatitis B infection No known G6PD deficiency No history of allergic reactions attributed to compounds of similar chemical or biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used in this study No prior alvocidib No prior purine analog therapy No more than 1 prior treatment with a biologic or alkylating agent No other concurrent investigational agents

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph Flynn

Organizational Affiliation

Ohio State University Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ohio State University Comprehensive Cancer Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

We'll reach out to this number within 24 hrs