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

NCT01076556 | Terminated Phase 1

• 7 other identifiers: NCI-2011-01373OSU 09089CDR0000666448OSU-090898267P30CA016058U01CA076576
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

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

  Determined using the CTEP Active Version of the CTCAE.

  21 days

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

  Up to 5 years

Study Arms (1)

Treatment (rituximab, cyclophosphamide, alvocidib)

EXPERIMENTAL

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).

Drug: Alvocidib Hydrochloride; Drug: Cyclophosphamide; Other: Diagnostic Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Rituximab

Interventions

Alvocidib Hydrochloride DRUG

Given IV

Also known as: 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

Treatment (rituximab, cyclophosphamide, alvocidib)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (rituximab, cyclophosphamide, alvocidib)

Diagnostic Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (rituximab, cyclophosphamide, alvocidib)

Pharmacological Study OTHER

Correlative studies

Treatment (rituximab, cyclophosphamide, alvocidib)

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Treatment (rituximab, cyclophosphamide, alvocidib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• p deletion
• q 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic

Interventions

cytokine inducible SH2-containing protein; alvocidib; Cyclophosphamide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joseph Flynn

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2010
• First Posted: February 26, 2010
• Study Start: April 1, 2010
• Primary Completion: July 1, 2010
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

US (1)