Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

NCT00946023 | Terminated Phase 2 Results DMC

• 2 other identifiers: J0941NA_00025589
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.

Conditions

Lymphoma; B-cell Lymphoma; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Keywords

lymphoma; non hodgkin lymphoma; allogeneic; bone marrow transplantation; nonmyeloablative; cyclophosphamide; rituximab

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Percentage of participants alive and without relapse or disease progression.

  1 year post-intervention

Secondary Outcomes (11)

• Progression-free Survival

  2 years post-intervention

• Overall Survival

  1 year post intervention

• Overall Survival

  2 years post intervention

• Relapse

  1 year post intervention

• Relapse

  2 years post intervention

Study Arms (1)

Transplant

EXPERIMENTAL

Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Rituximab; Biological: Allogeneic Bone Marrow Transplant (BMT)

Interventions

Fludarabine DRUG

Days -6 through -2: 30 mg/m\^2 IV daily

Also known as: Fludara

Transplant

Cyclophosphamide DRUG

Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily

Also known as: Cytoxan, CTX, Cy

Transplant

Total body irradiation RADIATION

Day -1: 200 centigray (cGy) in a single fraction

Also known as: TBI

Transplant

Tacrolimus DRUG

Start on Day 5 through Day 180

Also known as: FK-506, FK506, Prograf

Transplant

Mycophenolate Mofetil DRUG

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Also known as: MMF, CellCept

Transplant

Rituximab DRUG

Day 30 and every week after for 8 total doses: 375 mg/m\^2 IV

Also known as: Rituxan

Transplant

Allogeneic Bone Marrow Transplant (BMT) BIOLOGICAL

Day 0: Donor bone marrow infusion

Transplant

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Poor-risk CD20+, B-cell lymphoma, as follows:
• Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion (if histologic conversion, PR or CR is required):
• Follicular grade 1 or 2 lymphoma
• Follicular lymphoma not otherwise specified
• Marginal zone (or MALT) lymphoma
• Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
• Hairy cell leukemia
• Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
• Low grade B-cell lymphoma, unspecified
• Nodular lymphocyte-predominant Hodgkin lymphoma
• Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR is required)
• Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:
• Follicular grade 3 lymphoma
• Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma
• Mantle cell lymphoma

You may not qualify if:

• More than 20% involvement of bone marrow by chronic lymphocytic leukemia
• Active central nervous system lymphoma
• ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and 4)
• HIV positive
• Pregnant or breastfeeding

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• Kanakry JA, Gocke CD, Bolanos-Meade J, Gladstone DE, Swinnen LJ, Blackford AL, Fuchs EJ, Huff CA, Borrello I, Matsui WH, Brodsky RA, Rosner GL, Shanbhag S, Luznik L, Jones RJ, Ambinder RF, Kasamon YL. Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors. Biol Blood Marrow Transplant. 2015 Dec;21(12):2115-2122. doi: 10.1016/j.bbmt.2015.07.012. Epub 2015 Jul 14.

  PMID: 26183076 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic 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; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Rich Ambinder, MD
• Organization: Johns Hopkins University

rambind1@jhmi.edu

4109558839

Study Officials

• Yvette L Kasamon, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2009
• First Posted: July 24, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: July 17, 2013
• Last Updated: August 27, 2018
• Results First Posted: July 24, 2018

Record last verified: 2018-07

Locations

US (1)