Lymphoma is one of the most common cancers in dogs. Injectable multi-drug chemotherapy remains the standard of care, and is associated with high response rates and meaningful prolongation of life. However, a minority of dogs with lymphoma are treated with injectable chemotherapy, in part due to an inability of non-specialty practices to safely handle these drugs. However, there are no established effective chemotherapy protocols for previously untreated canine lymphoma that do not involve drugs that require special handling. The primary objective of this study is to evaluate the safety and antitumor activity of a combination of the drugs asparaginase, procarbazine, prednisone, and lomustine (APPL) given to dogs with previously untreated lymphoma. Your dog will receive up to 2 injections of asparaginase subcutaneously (under the skin), and will receive oral lomustine, procarbazine and prednisone at home. They will be rechecked weekly for the first 4 weeks after starting then every 4 weeks thereafter. Visits will generally take about 1 hour. They will be eligible to continue receiving treatment as long as the drugs are tolerated and your dog is experiencing clinical benefit (disease stabilization or meaningful tumor shrinkage). Dogs experiencing a complete response (complete disappearance of all evidence of lymphoma) will receive a total of 5 every-4-week cycles of treatment, followed by monthly rechecks. Analysis for tumor response will be performed by direct tumor measurement. Standard bloodwork will be performed at each visit. The total volume of blood involved in each collection is approximately 2 teaspoons.