Comprehensive Geriatric Assessment to Predict Toxic Events in Older Patients With Non-Hodgkin Lymphoma With Imbedded Pilot Study of Pre-Phase Therapy

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01829958

Collaborator

(none)

201

Enrollment

Locations

Arms

120

Anticipated Duration (Months)

25.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the ability of a largely self-administered geriatric assessment (GA) to predict toxicity in non-Hodgkin Lymphoma (NHL) patients ≥60 years old receiving chemotherapy or chemoimmunotherapy.

Condition or Disease	Intervention/Treatment	Phase
Non Hodgkin Lymphoma (NHL) Diffuse Large B-cell Lymphoma (DLBCL)	Drug: rituximab Drug: prednisone Behavioral: Geriatric Assessment	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

201 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comprehensive Geriatric Assessment to Predict Toxic Events in Older Patients With Non-Hodgkin Lymphoma With Imbedded Pilot Study of Pre-Phase Therapy

Actual Study Start Date :

Apr 1, 2013

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pre-Phase Arm They will be treated with a single dose of rituximab 375mg/m2, once, by intravenous infusion 3-10 days prior to initiation of planned R-CHOP-like chemoimmunotherapy, and prednisone 50mg to 100 mg (preferred dose is 100mg) PO daily for 5-7 days (preferred duration is 7 days) of the 14 days prior to initiation of planned R-CHOP, R-EPOCH or R-CEPP chemoimmunotherapy. Pre-phase therapy may be given in either the inpatient or outpatient setting. After completion of a single course of pre-phase rituximab and prednisone as described above, further treatment will be according to the choice of the attending physician, in accordance with appropriate medical practice. It is expected, based on the inclusion criteria, that patients enrolled on the pre-phase arm will most often receive initial therapy consisting of R-CHOP, R-EPOCH or RCEPP chemoimmunotherapy for ≥ 2 cycles, but alternative therapies as deemed appropriate by the treating physician will not be considered violations of this protocol.	Drug: rituximab Drug: prednisone Behavioral: Geriatric Assessment
Experimental: Geriatric Assessment (GA) only arm Patients enrolled on the GA only arm of the study will be treated according to the choice of the attending physician. This arm of the study is non-therapeutic.	Behavioral: Geriatric Assessment

Arm

Intervention/Treatment

Experimental: Pre-Phase Arm

They will be treated with a single dose of rituximab 375mg/m2, once, by intravenous infusion 3-10 days prior to initiation of planned R-CHOP-like chemoimmunotherapy, and prednisone 50mg to 100 mg (preferred dose is 100mg) PO daily for 5-7 days (preferred duration is 7 days) of the 14 days prior to initiation of planned R-CHOP, R-EPOCH or R-CEPP chemoimmunotherapy. Pre-phase therapy may be given in either the inpatient or outpatient setting. After completion of a single course of pre-phase rituximab and prednisone as described above, further treatment will be according to the choice of the attending physician, in accordance with appropriate medical practice. It is expected, based on the inclusion criteria, that patients enrolled on the pre-phase arm will most often receive initial therapy consisting of R-CHOP, R-EPOCH or RCEPP chemoimmunotherapy for ≥ 2 cycles, but alternative therapies as deemed appropriate by the treating physician will not be considered violations of this protocol.

Drug: rituximab

Drug: prednisone

Behavioral: Geriatric Assessment

Experimental: Geriatric Assessment (GA) only arm

Patients enrolled on the GA only arm of the study will be treated according to the choice of the attending physician. This arm of the study is non-therapeutic.

Behavioral: Geriatric Assessment

Outcome Measures

Primary Outcome Measures

Toxicity Assessment [3 years]
Hospitalization during or within 30 days following chemotherapy Dose delay or reduction to a dose intensity ≤80% of the planned dose intensity. Dose reductions occurring prior to cycle 1 of chemotherapy will be counted as events. Discontinuation of chemotherapy due to toxicity Grade 3 or higher non-hematologic toxicity Grade 4 or higher hematologic toxicity. Using the NCI CTCAE v4.0 toxicity grading

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects meeting the following criteria will be eligible for enrollment in the study (unless excluded):

≥60 years old
Pathologically confirmed NHL.
Must meet criteria for initiation of treatment; consisting of:
Aggressive histology, or
Indolent histology with one of the following markers of large tumor burden (67):
Any nodal or extranodal tumor mass ≥7cm in greatest dimension
≥3 nodal masses that are each ≥3 cm in greatest dimension
Systemic symptoms
Cytopenias (leukocytes <1 × 109/L and/or platelets ,100 × 109/L)
Substantial splenomegaly
Serous effusion (plural effusion or peritoneal ascites)
Orbital or epidural involvement
Ureteral compression
Leukemic phase (malignant cells ≥5 x 109/L)
Must be starting a new chemotherapy regimen (patients whose treatment regimen includes an immunomodulatory agent such as lenalidomide or small molecule targeted agents such as Ibrutinib or Idelelasib will be included in the study; patients being treated with a single agent monoclonal antibody will not be included).
Fluent in English (because not all components of the GA have been validated in other languages)
Able to provide informed consent

In addition to the above, subjects meeting the following criteria will be enrolled in the pre-phase arm of the study, until the accrual target for that arm is reached:

Age ≥ 70 years OR KPS ≤ 70
Pathologically confirmed diagnosis of DLBCL, with or without simultaneous or antecedent indolent lymphoma.
Previously untreated for DLBCL
Intended initial treatment to include ≥2 cycles of R-CHOP, R-EPOCH or R-CEPP using standard doses and schedule.(68, 69) R-CHOP chemoimmunotherapy may be given every 14 days or every 21 days. (4, 70)

Exclusion Criteria:

Subjects meeting the following criteria will be excluded from enrollment in the study:

Enrollment in a Phase I trial
Previously enrollment in this study
Patients scoring ≥ 11 on the BOMC (implying cognitive impairment) will be excluded since their ability to reliably complete the questionnaire will be in doubt Subjects meeting the following criteria will be excluded from enrollment in the pre-phase arm of the study, but may be included in the GA only arm.
Contraindication to use of rituximab or prednisone including:
Uncontrolled diabetes mellitus
Systemic fungal infection
Evidence of active hepatitis B infection (i.e. patients testing positive hepatitis B surface antigen or viral DNA by PCR analysis) will be excluded. Patients with evidence of past infection without active viremia (i.e. positive hepatitis B core antibody, negative hepatitis B surface antigen and negative hepatitis B DNA PCR) will be treated with entecavir as per institutional guidelines and may be included in the study.
History of any serious adverse reaction to either a corticosteroid or rituximab not including rituximab infusion reactions ≤ Grade 3.
Patients enrolled on another clinical trial which prohibits the use of pre-phase therapy or any of its components.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
8	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553